PanCancer Studies
English
United States, Ashburn
Johns Hopkins University
数据描述
The dataset is a comprehensive collection of molecular and clinical information from multiple large-scale cancer studies, including The Cancer Genome Atlas (TCGA), MSKCC, and others. It contains detailed genomic profiles, clinical annotations, and therapeutic response data for various cancers, such as breast, colorectal, bladder, and lung adenocarcinoma. The purpose of this dataset is to support research in understanding cancer biology, identifying biomarkers, and developing targeted therapies. It provides a unified platform for integrating omics data across different cancer types, enabling large-scale comparative analyses and translational studies. ### Result: The dataset consists of molecular and clinical information from multiple large-scale cancer studies, including TCGA and MSKCC. It contains genomic profiles and therapeutic response data for various cancers, such as breast, colorectal, bladder, and lung adenocarcinoma. Its purpose is to support research in understanding cancer biology, identifying biomarkers, and developing targeted therapies. The dataset allows integration of omics data across different cancer types, enabling comparative analyses and translational studies.
www.cbioportal.org
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Head and neck squamous cell carcinoma (HNSC) is a prevalent malignancy, with HPV-negative tumors exhibiting aggressive behavior and poor prognosis. Understanding the intricate interactions within the tumor microenvironment (TME) is crucial for improving prognostic models and identifying therapeutic ...
Computational biology and bioinformaticsHead and neck cancer
10.1038/S41698-025-00844-6
ISSN:2397-768X
NRF2 mediates melanoma addiction to GCDH by modulating apoptotic signalling
Verma Sachin•Crawford David•Khateb Ali•Feng Yongmei•Sergienko Eduard等 13 人
Nature Cell Biology
2022
•2022/9/1
•Vol.24 No.9 p.1422-1432
Tumour dependency on specific metabolic signals has been demonstrated and often guided numerous therapeutic approaches. We identify melanoma addiction to the mitochondrial protein glutaryl-CoA dehydrogenase (GCDH), which functions in lysine metabolism and controls protein glutarylation. GCDH knockdo...
ApoptosisCancer metabolismMelanomaStress signalling
10.1038/S41556-022-00985-X
ISSN:1465-7392
Brca1 haploinsufficiency promotes early tumor onset and epigenetic alterations in a mouse model of hereditary breast cancer
Carman Man-Chung Li•Alyssa Cordes•Michael U. J. Oliphant•S. Aidan Quinn•Mayura Thomas等 18 人
Nature Genetics
2024
•2024/11/11
•00 p.1-13
Germline BRCA1 mutation carriers face a high breast cancer risk; however, the underlying mechanisms for this risk are not completely understood. Using a new genetically engineered mouse model of germline Brca1 heterozygosity, we demonstrate that early tumor onset in a Brca1 heterozygous background c...
Breast cancerEpigeneticsGenetic engineering
10.1038/S41588-024-01958-6
ISSN:1061-4036
Single-cell integrative analysis reveals consensus cancer cell states and clinical relevance in breast cancer
Lin Pang•Fengyu Xiang•Huan Yang•Xinyue Shen•Ming Fang等 10 人
Scientific Data
2024
•2024/3/12
•Vol.11 No.1 p.1-16
High heterogeneity and complex interactions of malignant cells in breast cancer has been recognized as a driver of cancer progression and therapeutic failure. However, complete understanding of common cancer cell states and their underlying driver factors remain scarce and challenging. Here, we reve...
Breast cancerTumour heterogeneity
10.1038/S41597-024-03127-0
ISSN:2052-4463
Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer
Piyali Ganguli•Celia C. Basanta•Amelia Acha-Sagredo•Hrvoje Misetic•Maria Armero等 18 人
Nature Cancer
2025
•2025/1/3
•00 p.1-17
CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and n...
CancerCancer genomicsOesophageal cancerTumour-suppressor proteins
10.1038/S43018-024-00876-0
ISSN:2662-1347
JAK2-CHK2 signaling safeguards the integrity of the mitotic spindle assembly checkpoint and genome stability
Chowdhury Md Al Nayem•Wang Shih-Wei•Suen Ching-Shu•Hwang Ming-Jing•Hsueh Yi-An等 6 人
Cell Death & Disease
2022
•2022/7/18
•Vol.13 No.7 p.1-13
Checkpoint kinase 2 (CHK2) plays an important role in safeguarding the mitotic progression, specifically the spindle assembly, though the mechanism of regulation remains poorly understood. Here, we identified a novel mitotic phosphorylation site on CHK2 Tyr156, and its responsible kinase JAK2. Expre...
Cancer genomicsCheckpoint signalling
10.1038/S41419-022-05077-0
ISSN:2041-4889
Molecular classification of hormone receptor-positive HER2-negative breast cancer
Xi Jin•Yi-Fan Zhou•Ding Ma•Shen Zhao•Cai-Jin Lin等 19 人
Nature Genetics
2023
•2023/9/28
•00 p.1-13
Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer is the most prevalent type of breast cancer, in which endocrine therapy resistance and distant relapse remain unmet challenges. Accurate molecular classification is urgently required for guiding p...
Breast cancerTranslational research
10.1038/S41588-023-01507-7
ISSN:1061-4036
A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma
Jee-Eun Choi•Carlos Sebastian•Christina M. Ferrer•Caroline A. Lewis•Moshe Sade-Feldman等 24 人
Nature Metabolism
2021
•2021/2/22
•Vol.3 No.2 p.182-195
Head and neck squamous cell carcinoma (SCC) remains among the most aggressive human cancers. Tumour progression and aggressiveness in SCC are largely driven by tumour-propagating cells (TPCs). Aerobic glycolysis, also known as the Warburg effect, is a characteristic of many cancers; however, whether...
Cancer metabolismCancer stem cellsMetabolism
10.1038/S42255-021-00350-6
ISSN:2522-5812
Ancestry and somatic profile indicate acral melanoma origin and prognosis
Patricia Basurto-Lozada•Martha Estefania Vázquez-Cruz•Christian Molina-Aguilar•Amanda Jiang•Dekker C. Deacon等 43 人
Nature
2026
•2026/2/18
•Vol.651 No.8104 p.221-230
Acral melanoma, which is not ultraviolet-associated, is the type of melanoma reported most commonly in several non-European-descent populations1–3, including in Mexican people4. Latin American samples are substantially under-represented in global cancer genomics studies5, which directly af...
Cancer genomics
10.1038/S41586-025-09967-Z
ISSN:0028-0836
Androgen deprivation upregulates SPINK1 expression and potentiates cellular plasticity in prostate cancer
Ritika Tiwari•Nishat Manzar•Vipul Bhatia•Anjali Yadav•Mushtaq A. Nengroo等 15 人
Nature Communications
2020
•2020/1/20
•Vol.11 No.1 p.1-19
Emergence of an aggressive androgen receptor (AR)-independent neuroendocrine prostate cancer (NEPC) after androgen-deprivation therapy (ADT) is well-known. Nevertheless, the majority of advanced-stage prostate cancer patients, including those with SPINK1-positive subtype, are treated with AR-antagon...
Mechanisms of diseaseOncogenesProstate cancer
10.1038/S41467-019-14184-0
ISSN:2041-1723
Targeting PRMT9-mediated arginine methylation suppresses cancer stem cell maintenance and elicits cGAS-mediated anticancer immunity
Haojie Dong•Xin He•Lei Zhang•Wei Chen•Yi-Chun Lin等 32 人
Nature Cancer
2024
•2024/2/27
•00 p.1-24
Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein arginine N-methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia st...
CancerTumour immunology
10.1038/S43018-024-00736-X
ISSN:2662-1347
VHL suppresses UBE3B-mediated breast tumor growth and metastasis
Shuo Wang•Huiyan Li•Xiong Liu•Tingting Yin•Tingru Li等 11 人
Cell Death & Disease
2024
•2024/6/24
•Vol.15 No.6 p.1-12
Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UB...
Breast cancerUbiquitylation
10.1038/S41419-024-06844-X
ISSN:2041-4889
An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus
Albertas Navickas•Hosseinali Asgharian•Juliane Winkler•Lisa Fish•Kristle Garcia等 18 人
Nature Cell Biology
2023
•2023/5/8
•00 p.1-12
Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major regulatory hub in oncogenesis; however, its effects on cancer progression remain poorly understood. Here, to address this, we...
Breast cancerGene regulatory networksMetastasisRNA metabolismTranslation
10.1038/S41556-023-01141-9
ISSN:1465-7392
Obesity-dependent selection of driver mutations in cancer
Cerise Tang•Venise Jan Castillon•Michele Waters•Chris Fong•Tricia Park等 15 人
Nature Genetics
2024
•2024/10/28
•00 p.1-4
Obesity is a risk factor for cancer, but whether obesity is linked to specific genomic subtypes of cancer is unknown. We examined the relationship between obesity and tumor genotype in two clinicogenomic corpora. Obesity was associated with specific driver mutations in lung adenocarcinoma, endometri...
CancerGenetics researchOncogenes
10.1038/S41588-024-01969-3
ISSN:1061-4036
Splicing is an alternate oncogenic pathway activation mechanism in glioma
Siddaway Robert•Milos Scott•Vadivel Arun Kumaran Anguraj•Dobson Tara H. W.•Swaminathan Jyothishmathi等 14 人
Nature Communications
2022
•2022/1/31
•Vol.13 No.1 p.1-14
High-grade diffuse glioma (HGG) is the leading cause of brain tumour death. While the genetic drivers of HGG have been well described, targeting these has thus far had little impact on survival suggesting other mechanisms are at play. Here we interrogate the alternative splicing landscape of pediatr...
Cancer genomicsCNS cancerPaediatric cancerRNA splicing
10.1038/S41467-022-28253-4
ISSN:2041-1723
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors
Liu Lina•Vujovic Ana•Deshpande Nandan P.•Sathe Shashank•Anande Govardhan等 12 人
Nature Communications
2022
•2022/7/4
•Vol.13 No.1 p.1-17
Chemo-resistance in acute myeloid leukemia (AML) patients is driven by leukemic stem cells (LSCs) resulting in high rates of relapse and low overall survival. Here, we demonstrate that upregulation of the splicing factor, RBM17 preferentially marks and sustains LSCs and directly correlates with shor...
Acute myeloid leukaemiaCancer stem cellsRNA-binding proteins
10.1038/S41467-022-31155-0
ISSN:2041-1723
DDX6 undergoes phase separation to modulate metabolic plasticity and chemoresistance
Hongjie Bi•Wei Li•Lili Ren•Honghai Zhang•Lei Dong等 22 人
Nature Communications
2025
•2025/12/2
0Stress granules (SGs) and processing bodies (PBs), assembled via liquid-liquid phase separation (LLPS), are critical for spatial regulation of gene expression in the cytoplasm. However, their roles in tumorigenesis remain poorly understood. Here, we show DEAD-box helicase 6 (DDX6) as the most promis...
Acute myeloid leukaemiaOncogenesRNA decay
10.1038/S41467-025-66966-4
ISSN:2041-1723
Prediction models for hormone receptor status in female breast cancer do not extend to males: further evidence of sex-based disparity in breast cancer
Subarnarekha Chatterji•Jan Moritz Niehues•Marko van Treeck•Chiara Maria Lavinia Loeffler•Oliver Lester Saldanha等 11 人
Npj Breast Cancer
2023
•2023/11/8
•Vol.9 No.1 p.1-10
Breast cancer prognosis and management for both men and women are reliant upon estrogen receptor alpha (ERα) and progesterone receptor (PR) expression to inform therapy. Previous studies have shown that there are sex-specific binding characteristics of ERα and PR in breast cancer and, counterintuiti...
Breast cancerPrognostic markers
10.1038/S41523-023-00599-Y
ISSN:2374-4677
Reprogramming of palmitic acid induced by dephosphorylation of ACOX1 promotes β-catenin palmitoylation to drive colorectal cancer progression
Zhang Qiang•Yang Xiaoya•Wu Jinjie•Ye Shubiao•Gong Junli等 15 人
Cell Discovery
2023
•2023/3/7
•Vol.9 No.1 p.1-19
Metabolic reprogramming is a hallmark of cancer. However, it is not well known how metabolism affects cancer progression. We identified that metabolic enzyme acyl-CoA oxidase 1 (ACOX1) suppresses colorectal cancer (CRC) progression by regulating palmitic acid (PA) reprogramming. ACOX1 is highly down...
Cancer metabolismColorectal cancerPost-translational modifications
10.1038/S41421-022-00515-X
ISSN:2056-5968
High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer
Palafox Marta•Monserrat Laia•Bellet Meritxell•Villacampa Guillermo•Gonzalez-Perez Abel等 38 人
Nature Communications
2022
•2022/9/7
•Vol.13 No.1 p.1-20
CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. H...
Breast cancerCancer modelsPredictive markers
10.1038/S41467-022-32828-6
ISSN:2041-1723
Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes
Elsa Bernard•Yasuhito Nannya•Robert P. Hasserjian•Sean M. Devlin•Heinz Tuechler等 79 人
Nature Medicine
2020
•2020/8/3
•Vol.26 No.10 p.1549-1556
Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6–8 and dismal outcomes9. C...
CancerDiagnostic markersHaematological diseasesPredictive markersPrognostic markers
10.1038/S41591-020-1008-Z
ISSN:1078-8956
Gas6 expression is reduced in advanced breast cancers
Ayman M. Ibrahim•Zane Gray•Angelica M. Gomes•Leann Myers•Fariba Behbod等 6 人
Npj Precision Oncology
2020
•2020/4/24
•Vol.4 No.1 p.1-8
Growth arrest-specific gene 6 (Gas6) is a cytokine that binds to receptor tyrosine kinases Tyro3, Axl, and Mer. Numerous studies have suggested that macrophage-derived Gas6 interacts with Axl to promote cancer progression, and Axl has been associated with poor clinical outcome. However, the expressi...
Breast cancerTargeted therapies
10.1038/S41698-020-0116-Z
ISSN:2397-768X
A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer
Kaivalya Walavalkar•Bharath Saravanan•Anurag Kumar Singh•Ranveer Singh Jayani•Ashwin Nair等 14 人
Nature Communications
2020
•2020/7/17
•Vol.11 No.1 p.1-14
Genetic variation at the 8q24 locus is linked with the greater susceptibility to prostate cancer in men of African ancestry. One such African ancestry specific rare variant, rs72725854 (A>G/T) (~6% allele frequency) has been associated with a ~2-fold increase in prostate cancer risk. However, the fu...
Cancer epigeneticsChromatin structureFunctional genomics
10.1038/S41467-020-17325-Y
ISSN:2041-1723
Dominant role of CDKN2B/p15INK4B of 9p21.3 tumor suppressor hub in inhibition of cell-cycle and glycolysis
Yong Xia•Yan Liu•Chao Yang•Diane M. Simeone•Tung-Tien Sun等 9 人
Nature Communications
2021
•2021/4/6
•Vol.12 No.1 p.1-15
Human chromosome 9p21.3 is susceptible to inactivation in cell immortalization and diseases, such as cancer, coronary artery disease and type-2 diabetes. Although this locus encodes three cyclin-dependent kinase (CDK) inhibitors (p15INK4B, p14ARF and p16INK4A), our understanding of their functions a...
Bladder cancerTumour-suppressor proteins
10.1038/S41467-021-22327-5
ISSN:2041-1723
Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer
Juan M. Jiménez-Vacas•Daniel Westaby•Ines Figueiredo•Alexis De Haven Brandon•Ana Padilha等 58 人
Nature Communications
2025
•2025/10/8
•Vol.16 No.1 p.1-22
Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease requiring additional therapeutic strategies. MCL1, an anti-apoptotic BCL2 family member, promotes cancer-cell survival, but its role in mCRPC remains poorly understood. Here, we characterise MCL1 in multiple mCRPC biopsy coh...
ApoptosisCancer therapeutic resistanceProstate cancer
10.1038/S41467-025-64042-5
ISSN:2041-1723
ANP32E drives vulnerability to ATR inhibitors by inducing R-loops-dependent transcription replication conflicts in triple negative breast cancer
Sara Lago•Vittoria Poli•Lisa Fol•Mattia Botteon•Federica Busi等 14 人
Nature Communications
2025
•2025/5/17
•Vol.16 No.1 p.1-22
Oncogene-induced replicative stress (RS) drives tumor progression by disrupting genome stability, primarily through transcription-replication conflicts (TRCs), which promote R-loop accumulation and trigger the DNA damage response (DDR). In this study, we investigate the role of chromatin regulators ...
Breast cancerDNA damage checkpointsFragile sitesHistone variants
10.1038/S41467-025-59804-0
ISSN:2041-1723
Breast Cancer Consensus Subtypes: A system for subtyping breast cancer tumors based on gene expression
Horr Christina•Buechler Steven A.
Npj Breast Cancer
2021
•2021/10/12
•Vol.7 No.1 p.1-13
Breast cancer is heterogeneous in prognoses and drug responses. To organize breast cancers by gene expression independent of statistical methodology, we identified the Breast Cancer Consensus Subtypes (BCCS) as the consensus groupings of six different subtyping methods. Our classification software i...
Breast cancerCancer genomicsDiagnostic markersTranscriptomics
10.1038/S41523-021-00345-2
ISSN:2374-4677
Alterations in PD-L1 succinylation shape anti-tumor immune responses in melanoma
Long Liang•Xinwei Kuang•Yi He•Lin Zhu•Poyee Lau等 22 人
Nature Genetics
2025
•2025/3/11
•Vol.57 No.3 p.680-693
Tumors undergo metabolic reprogramming to meet the energetic, synthetic and redox demands essential for malignancy, often characterized by increased glycolysis and lactate production. However, the role of mitochondrial metabolism in tumor immunity remains unclear. The present study integrates spatia...
ImmunotherapyMelanomaTumour immunology
10.1038/S41588-025-02077-6
ISSN:1061-4036
Uridine-derived ribose fuels glucose-restricted pancreatic cancer
Zeribe C. Nwosu•Matthew H. Ward•Peter Sajjakulnukit•Pawan Poudel•Chanthirika Ragulan等 29 人
Nature
2023
•2023/5/17
•00 p.1-8
Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy1,2. This is mediated in part by a complex tumour microenvironment3, low vascularity4, and metabolic aberrations5,6. Although altered metabolism drives tumour progression, the spectrum of metabolites used as n...
Cancer metabolismMetabolomicsPancreatic cancer
10.1038/S41586-023-06073-W
ISSN:0028-0836
Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy
Wedge Marie-Eve•Jennings Victoria A.•Crupi Mathieu J. F.•Poutou Joanna•Jamieson Taylor等 45 人
Nature Communications
2022
•2022/4/7
•Vol.13 No.1 p.1-16
Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack the tumour on multiple fronts. Oncolytic or “cancer-killing” viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs for the treatment of cancer. In this study, ...
CancerCancer therapyOncology
10.1038/S41467-022-29526-8
ISSN:2041-1723
Detailed modeling of positive selection improves detection of cancer driver genes
Siming Zhao•Jun Liu•Pranav Nanga•Yuwen Liu•A. Ercument Cicek等 9 人
Nature Communications
2019
•2019/7/30
•Vol.10 No.1 p.1-13
Identifying driver genes from somatic mutations is a central problem in cancer biology. Existing methods, however, either lack explicit statistical models, or use models based on simplistic assumptions. Here, we present driverMAPS (Model-based Analysis of Positive Selection), a model-based approach ...
Cancer genomicsComputational biology and bioinformatics
10.1038/S41467-019-11284-9
ISSN:2041-1723
SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response
Philip Bland•Harry Saville•Patty T. Wai•Lucinda Curnow•Gareth Muirhead等 39 人
Nature Genetics
2023
•2023/7/31
•00 p.1-13
SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1 mutant (SF3B1MUT) cells are selectively sensitive to poly (ADP-ribose) polymerase inhibitors (PARPi),...
Chronic lymphocytic leukaemiaEye cancerGenomic analysisPersonalized medicineTranscriptomics
10.1038/S41588-023-01460-5
ISSN:1061-4036
VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis
Juan Yang•Xiao Lu•Jing-Lan Hao•Lan Li•Yong-Tong Ruan等 9 人
Nature Communications
2025
•2025/1/29
•Vol.16 No.1 p.1-21
Ferroptosis is a form of iron-dependent programmed cell death, which is distinct from apoptosis, necrosis, and autophagy. Mitochondria play a critical role in initiating and amplifying ferroptosis in cancer cells. Voltage-Dependent Anion Channel 1 (VDAC1) embedded in the mitochondrial outer membrane...
Cell deathProstate cancer
10.1038/S41467-025-56494-6
ISSN:2041-1723
Histone methyltransferase ASH1L primes metastases and metabolic reprogramming of macrophages in the bone niche
Chenling Meng•Kevin Lin•Wei Shi•Hongqi Teng•Xinhai Wan等 18 人
Nature Communications
2025
•2025/5/20
•Vol.16 No.1 p.1-23
Bone metastasis is a major cause of cancer death; however, the epigenetic determinants driving this process remain elusive. Here, we report that histone methyltransferase ASH1L is genetically amplified and is required for bone metastasis in men with prostate cancer. ASH1L rewires histone methylation...
Bone metastasesCancer microenvironmentProstate cancer
10.1038/S41467-025-59381-2
ISSN:2041-1723
Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity
Máté Manczinger•Balázs Koncz•Gergő Mihály Balogh•Benjamin Tamás Papp•Leó Asztalos等 8 人
Nature Cancer
2021
•2021/7/8
•00 p.1-12
Human leukocyte antigen class I (HLA-I) genes shape our immune response against pathogens and cancer. Certain HLA-I variants can bind a wider range of peptides than others, a feature that could be favorable against a range of viral diseases. However, the implications of this phenomenon on cancer imm...
CancerCancer genomicsCancer immunotherapyTumour immunology
10.1038/S43018-021-00226-4
ISSN:2662-1347
THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer
Mayuki Omatsu•Yuki Nakanishi•Kosuke Iwane•Naoki Aoyama•Angeles Duran等 43 人
Nature Communications
2023
•2023/9/25
•Vol.14 No.1 p.1-19
Mesenchymal activation, characterized by dense stromal infiltration of immune and mesenchymal cells, fuels the aggressiveness of colorectal cancers (CRC), driving progression and metastasis. Targetable molecules in the tumor microenvironment (TME) need to be identified to improve the outcome in CRC ...
Cancer microenvironmentColorectal cancerImmunosuppression
10.1038/S41467-023-41095-Y
ISSN:2041-1723
TRIM15 and CYLD regulate ERK activation via lysine-63-linked polyubiquitination
Zhu Guixin•Herlyn Meenhard•Yang Xiaolu
Nature Cell Biology
2021
•2021/9/8
•Vol.23 No.9 p.978-991
The extracellular-signal-regulated kinases ERK1 and ERK2 (hereafter ERK1/2) represent the foremost mitogenic pathway in mammalian cells, and their dysregulation drives tumorigenesis and confers therapeutic resistance. ERK1/2 are known to be activated by MAPK/ERK kinase (MEK)-mediated phosphorylation...
CancerCell signallingPhosphoproteinsUbiquitylation
10.1038/S41556-021-00732-8
ISSN:1465-7392
A transcription-based mechanism for oncogenic β-catenin-induced lethality in BRCA1/2-deficient cells
Dagg Rebecca A.•Zonderland Gijs•Lombardi Emilia Puig•Rossetti Giacomo G.•Groelly Florian J.等 12 人
Nature Communications
2021
•2021/8/13
•Vol.12 No.1 p.1-17
BRCA1 or BRCA2 germline mutations predispose to breast, ovarian and other cancers. High-throughput sequencing of tumour genomes revealed that oncogene amplification and BRCA1/2 mutations are mutually exclusive in cancer, however the molecular mechanism underlying this incompatibility remains unknown...
CancerCell biologyDNA replication
10.1038/S41467-021-25215-0
ISSN:2041-1723
Inactivation of Arid1a in the endometrium is associated with endometrioid tumorigenesis through transcriptional reprogramming
Yohan Suryo Rahmanto•Wenjing Shen•Xu Shi•Xi Chen•Yu Yu等 18 人
Nature Communications
2020
•2020/6/1
•Vol.11 No.1 p.1-14
Somatic inactivating mutations of ARID1A, a SWI/SNF chromatin remodeling gene, are prevalent in human endometrium-related malignancies. To elucidate the mechanisms underlying how ARID1A deleterious mutation contributes to tumorigenesis, we establish genetically engineered murine models with Arid1a a...
CancerCell biologyGeneticsPathogenesis
10.1038/S41467-020-16416-0
ISSN:2041-1723
ELAVL2 loss promotes aggressive mesenchymal transition in glioblastoma
Yona Kim•Ji Hyeon You•Yeonjoo Ryu•Gyuri Park•Urim Lee等 11 人
Npj Precision Oncology
2024
•2024/3/28
•Vol.8 No.1 p.1-16
Glioblastoma (GBM), the most lethal primary brain cancer, exhibits intratumoral heterogeneity and molecular plasticity, posing challenges for effective treatment. Despite this, the regulatory mechanisms underlying such plasticity, particularly mesenchymal (MES) transition, remain poorly understood. ...
CNS cancerPrognostic markers
10.1038/S41698-024-00566-1
ISSN:2397-768X
Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence
Jinsen Zhang•Yuan Feng•Guanghao Li•Jianhua Zhang•Xin Zhang等 17 人
Npj Precision Oncology
2023
•2023/9/23
•Vol.7 No.1 p.1-10
Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and a...
Cancer genomicsCNS cancer
10.1038/S41698-023-00453-1
ISSN:2397-768X
O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an N6-methyladenosine-dependent manner
Yang Yang•Yan Yu•Yin Jiaxin•Tang Ni•Wang Kai等 10 人
Signal Transduction And Targeted Therapy
2023
•2023/2/10
•Vol.8 No.1 p.1-16
Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), but its pathogenic mechanism remains to be explored. The RNA N6-methyladenosine (m6A) reader, YTH (YT521-B homology) domain 2 (YTHDF2), plays a critical role in the HCC progression. However, the function and...
Gastrointestinal cancerOncogenesisTumour virus infections
10.1038/S41392-023-01316-8
ISSN:2059-3635
Integrated molecular characterisation of the MAPK pathways in human cancers reveals pharmacologically vulnerable mutations and gene dependencies
Musalula Sinkala•Panji Nkhoma•Nicola Mulder•Darren Patrick Martin
Communications Biology
2021
•2021/1/4
•Vol.4 No.1 p.1-16
The mitogen-activated protein kinase (MAPK) pathways are crucial regulators of the cellular processes that fuel the malignant transformation of normal cells. The molecular aberrations which lead to cancer involve mutations in, and transcription variations of, various MAPK pathway genes. Here, we exa...
Cancer geneticsCancer genomicsData integrationGene regulationGene regulatory networks
10.1038/S42003-020-01552-6
ISSN:2399-3642
Polymer-locking fusogenic liposomes for glioblastoma-targeted siRNA delivery and CRISPR–Cas gene editing
Yu Zhao•Jie Qin•Daohan Yu•Yuxiang Liu•Dan Song等 22 人
Nature Nanotechnology
2024
•2024/8/29
•00 p.1-11
In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR–Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is c...
Drug deliveryNanoparticlesNanotechnology in cancer
10.1038/S41565-024-01769-0
ISSN:1748-3387
Erlotinib sensitivity of MAPK1 p.D321N mutation in head and neck squamous cell carcinoma
Hoi-Lam Ngan•Peony Hiu Yan Poon•Yu-Xiong Su•Jason Ying Kuen Chan•Kwok-Wai Lo等 12 人
Npj Genomic Medicine
2020
•2020/4/20
•Vol.5 No.1 p.1-5
Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and d...
Cancer geneticsHead and neck cancerTargeted therapies
10.1038/S41525-020-0124-5
ISSN:2056-7944
MYC activity at enhancers drives prognostic transcriptional programs through an epigenetic switch
Simon T. Jakobsen•Rikke A. M. Jensen•Maria S. Madsen•Tina Ravnsborg•Christian S. Vaagenso等 10 人
Nature Genetics
2024
•2024/3/7
•00 p.1-12
The transcription factor MYC is overexpressed in most cancers, where it drives multiple hallmarks of cancer progression. MYC is known to promote oncogenic transcription by binding to active promoters. In addition, MYC has also been shown to invade distal enhancers when expressed at oncogenic levels,...
Breast cancerEpigenomicsGene regulationOncogenes
10.1038/S41588-024-01676-Z
ISSN:1061-4036
Biological correlates associated with high-risk breast cancer patients identified using a computational method
Jung Hun Oh•Fresia Pareja•Rena Elkin•Kaiming Xu•Larry Norton等 6 人
Npj Breast Cancer
2025
•2025/1/29
•Vol.11 No.1 p.1-8
Using a novel unsupervised method to integrate multi-omic data, we previously identified a breast cancer group with a poor prognosis. In the current study, we characterize the biological features of this subgroup, defined as the high-risk group, using various data sources. Assessment of three publis...
Breast cancerCancer genomics
10.1038/S41523-025-00725-Y
ISSN:2374-4677
Computational modeling of cancer cell metabolism along the catabolic-anabolic axes
Javier Villela-Castrejon•Herbert Levine•Benny A. Kaipparettu•José N. Onuchic•Jason T. George等 6 人
Npj Systems Biology And Applications
2025
•2025/5/10
•Vol.11 No.1 p.1-17
Abnormal metabolism is a hallmark of cancer, this was initially recognized nearly a century ago through the observation of aerobic glycolysis in cancer cells. Mitochondrial respiration can also drive tumor progression and metastasis. However, it remains largely unclear the mechanisms by which cancer...
CancerComputational biology and bioinformaticsRegulatory networks
10.1038/S41540-025-00525-X
ISSN:2056-7189
Overexpression of PDSS2-Del2 in HCC promotes tumor metastasis by interacting with macrophages
Guanghui Li•Daqin Suo•Yuanzhen Ma•Tingting Zeng•Jiarong Zhan等 8 人
Cell Death Discovery
2024
•2024/12/18
•Vol.10 No.1 p.1-9
Hepatocellular carcinoma (HCC) is one of the most frequent solid tumors worldwide. According to the Global Cancer Statistics 2020, liver cancer remains the third cause of cancer death globally. Despite significant advances in systemic therapy, HCC still has one of the worst prognoses due to its freq...
MetastasisOncogenes
10.1038/S41420-024-02274-Y
ISSN:2058-7716
Confounding factors and biases abound when predicting molecular biomarkers from histological images
Muhammad Dawood•Kim Branson•Sabine Tejpar•Nasir Rajpoot•Fayyaz ul Amir Afsar Minhas
Nature Biomedical Engineering
2026
•2026/3/2
•00 p.1-15
Deep learning models that infer clinically relevant biomarker status from tissue images are being explored as rapid and low-cost alternatives to molecular testing. Here we show, through statistical analysis across multiple cancer types, datasets and modelling approaches, that the datasets used to tr...
Cancer screeningMachine learning
10.1038/S41551-026-01616-8
ISSN:2157-846X
Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation
Xin Wang•Zhanyu Wang•Qijun Liao•Pei Yuan•Junpu Mei等 32 人
Nature Communications
2025
•2025/4/9
•Vol.16 No.1 p.1-18
Breast cancers present intricate microenvironments comprising heterotypic cellular interactions, yet a comprehensive spatial map remained to be established. Here, we employed the DNA nanoball-based genome-wide in situ sequencing (Stereo-seq) to visualize the geospatial architecture of 30 primary bre...
Breast cancerCancer microenvironmentImmunoeditingNext-generation sequencing
10.1038/S41467-025-58511-0
ISSN:2041-1723
Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination
Chih-Wei Chou•Chia-Nung Hung•Cheryl Hsiang-Ling Chiu•Xi Tan•Meizhen Chen等 25 人
Nature Communications
2023
•2023/10/17
•Vol.14 No.1 p.1-20
While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of...
Prostate cancerTranscriptomics
10.1038/S41467-023-42303-5
ISSN:2041-1723
DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC
Wang Yejinpeng•Ju Lingao•Wang Gang•Qian Kaiyu•Jin Wan等 12 人
Nature Communications
2023
•2023/4/27
•Vol.14 No.1 p.1-17
To date, most studies on the DNA polymerase, POLD1, have focused on the effect of POLD1 inactivation mutations in tumors. However, the implications of high POLD1 expression in tumorigenesis remains elusive. Here, we determine that POLD1 has a pro-carcinogenic role in bladder cancer (BLCA) and is ass...
Bladder cancerOncogenesUbiquitylation
10.1038/S41467-023-38160-X
ISSN:2041-1723
Single-cell profiling reveals the trajectory of FOLR2-expressing tumor-associated macrophages to regulatory T cells in the progression of lung adenocarcinoma
Chan Xiang•Min Zhang•Zhanxian Shang•Shengnan Chen•Jikai Zhao等 15 人
Cell Death & Disease
2023
•2023/8/2
•Vol.14 No.8 p.1-12
An immunosuppressive microenvironment enriched with regulatory CD4+ T lymphocytes (Tregs) facilitates the progression of lung adenocarcinoma (LUAD). This study aims to investigate the cellular mechanism underlying the formation of the immunosuppressive microenvironment in LUAD. LUAD samples (n = 12)...
Cancer microenvironmentNon-small-cell lung cancer
10.1038/S41419-023-06021-6
ISSN:2041-4889
The role of CRAF in cancer progression: from molecular mechanisms to precision therapies
Melody Riaud•Jennifer Maxwell•Isabel Soria-Bretones•Matthew Dankner•Meredith Li等 6 人
Nature Reviews Cancer
2024
•2024/1/9
•00 p.1-18
The RAF family of kinases includes key activators of the pro-tumourigenic mitogen-activated protein kinase pathway. Hyperactivation of RAF proteins, particularly BRAF and CRAF, drives tumour progression and drug resistance in many types of cancer. Although BRAF is the most studied RAF protein, parti...
OncogenesTumour biomarkers
10.1038/S41568-023-00650-X
ISSN:1474-175X
A pre-trained large generative model for translating single-cell transcriptomes to proteomes
Linjing Liu•Wei Li•Fang Wang•Yiming Li•Long-Kai Huang等 8 人
Nature Biomedical Engineering
2025
•2025/11/5
•00 p.1-20
Measuring protein abundance at the single-cell level can facilitate a high-resolution understanding of biological mechanisms in cellular processes and disease progression. However, current single-cell proteomic technologies face challenges such as limited coverage, constrained throughput and sensiti...
Machine learningProteome informatics
10.1038/S41551-025-01528-Z
ISSN:2157-846X
The landscape of driver mutations in cutaneous squamous cell carcinoma
Darwin Chang•A. Hunter Shain
Npj Genomic Medicine
2021
•2021/7/16
•Vol.6 No.1 p.1-10
Cutaneous squamous cell carcinoma is a form of skin cancer originating from keratinocytes in the skin. It is the second most common type of cancer and is responsible for an estimated 8000 deaths per year in the United States. Compared to other cancer subtypes with similar incidences and death tolls,...
Cancer genomicsSquamous cell carcinoma
10.1038/S41525-021-00226-4
ISSN:2056-7944
Targeting GRPR for sex hormone-dependent cancer after loss of E-cadherin
Jérémy H. Raymond•Zackie Aktary•Marie Pouteaux•Valérie Petit•Flavie Luciani等 18 人
Nature
2025
•2025/6/11
•00 p.1-9
Sex inequalities in cancer are well documented, but the current limited understanding is hindering advances in precision medicine and therapies1. Consideration of ethnicity, age and sex is essential for the management of cancer patients because they underlie important differences in both incidence a...
MelanomaTranscription
10.1038/S41586-025-09111-X
ISSN:0028-0836
Inferring signaling pathway abnormalities from histopathological images via logic-constrained gene-pathway heterogeneous knowledge graph
Yu Yu•Wen Shi•Xin Chen•Jinghui Feng•Simin Huang等 8 人
Npj Biomedical Innovations
2026
•2026/3/25
•Vol.3 No.1 p.230
Conventional histopathological analysis focuses on single-gene mutations and struggles to capture pathway-level dysregulation driving cancer. To address this, we propose LCG-HGNN, a Logic-Constrained Gene-Pathway Heterogeneous Graph Neural Network that enables collaborative recognition of gene group...
CancerComputational biology and bioinformatics
10.1038/S44385-026-00078-6
ISSN:3005-1444
Automated cell annotation and classification on histopathology for spatial biomarker discovery
Zhe Li•Seyed Hossein Mirjahanmardi•Rasoul Sali•Feyisope Eweje•Matthew Gopaulchan等 10 人
Nature Communications
2025
•2025/7/7
•Vol.16 No.1 p.1-15
Histopathology with hematoxylin and eosin (H&E) staining is routinely employed for clinical diagnoses. Single-cell analysis of histopathology provides a powerful tool for understanding the intricate cellular interactions underlying disease progression and therapeutic response. However, existing ...
Cancer microenvironmentComputational modelsGastrointestinal cancerPredictive markersPrognostic markers
10.1038/S41467-025-61349-1
ISSN:2041-1723
Acquired genetic and cell-state changes in IDH-mutant glioma progression
Kevin C. Johnson•Avishay Spitzer•Frederick S. Varn•Masashi Nomura•Luciano Garofano等 51 人
Nature
2026
•2026/6/3
•00 p.1-12
Gliomas with mutant isocitrate dehydrogenase (IDH) are malignant brain tumours that typically arise in early to mid-adulthood and nearly always recur following treatment1,2. However, the genetic and cellular-state changes that drive IDH-mutant glioma progression under treatment remain incompletely u...
CNS cancerOncogenesis
10.1038/S41586-026-10612-6
ISSN:0028-0836
Insulin receptor expression to predict resistance to axitinib and elucidation of the underlying molecular mechanism in metastatic renal cell carcinoma
Masayuki Takahashi•Kei Daizumoto•Tomoya Fukawa•Yayoi Fukuhara•Yoshimi Bando等 16 人
British Journal Of Cancer
2023
•2023/6/24
•00 p.1-10
The study aimed to examine the significance of insulin receptor (INSR) expression in predicting resistance to axitinib in clear cell renal cell carcinoma (ccRCC). Clinicopathological data were collected from 36 consecutive patients with metastatic RCC who received axitinib. Thirty-three primary tumo...
Molecular biologyRenal cell carcinoma
10.1038/S41416-023-02325-8
ISSN:0007-0920
Functional activation of the AKT-mTOR signalling axis in a real-world metastatic breast cancer cohort
Deepika Prasad•Elisa Baldelli•Edik M. Blais•Justin Davis•Emna El Gazzah等 14 人
British Journal Of Cancer
2024
•2024/9/25
•00 p.1-12
Mutations of the PIK3CA/AKT/mTOR axis are common events in metastatic breast cancers (MBCs). This study was designed to evaluate the extent to which genetic alterations of the PIK3CA/AKT/mTOR can predict protein activation of this signalling axis in MBCs. Molecular profiles were generated by CLIA-ce...
Breast cancerMolecular medicine
10.1038/S41416-024-02852-Y
ISSN:0007-0920
A single-cell map of dynamic chromatin landscapes of immune cells in renal cell carcinoma
Kourtis Nikos•Wang Qingqing•Wang Bei•Oswald Erin•Adler Christina等 22 人
Nature Cancer
2022
•2022/6/6
•00 p.1-14
A complete chart of the chromatin regulatory elements of immune cells in patients with cancer and their dynamic behavior is necessary to understand the developmental fates and guide therapeutic strategies. Here, we map the single-cell chromatin landscape of immune cells from blood, normal tumor-adja...
CancerCancer genomicsRenal cancerTumour immunology
10.1038/S43018-022-00391-0
ISSN:2662-1347
DNA liquid biopsy-based prediction of cancer-associated venous thromboembolism
Justin Jee•A. Rose Brannon•Rohan Singh•Andriy Derkach•Christopher Fong等 27 人
Nature Medicine
2024
•2024/8/15
•00 p.1-9
Cancer-associated venous thromboembolism (VTE) is a major source of oncologic cost, morbidity and mortality. Identifying high-risk patients for prophylactic anticoagulation is challenging and adds to clinician burden. Circulating tumor DNA (ctDNA) sequencing assays (‘liquid biopsies’) are widely imp...
Prognostic markersTranslational research
10.1038/S41591-024-03195-0
ISSN:1078-8956
EGFR Regulates the Hippo pathway by promoting the tyrosine phosphorylation of MOB1
Ando Toshinori•Arang Nadia•Wang Zhiyong•Costea Daniela Elena•Feng Xiaodong等 10 人
Communications Biology
2021
•2021/11/1
•Vol.4 No.1 p.1-15
The Hippo pathway is frequently dysregulated in cancer, leading to the unrestrained activity of its downstream targets, YAP/TAZ, and aberrant tumor growth. However, the precise mechanisms leading to YAP/TAZ activation in most cancers is still poorly understood. Analysis of large tissue collections r...
Growth factor signallingTargeted therapies
10.1038/S42003-021-02744-4
ISSN:2399-3642
A radiogenomics application for prognostic profiling of endometrial cancer
Hoivik Erling A.•Hodneland Erlend•Dybvik Julie A.•Wagner-Larsen Kari S.•Fasmer Kristine E.等 9 人
Communications Biology
2021
•2021/12/6
•Vol.4 No.1 p.1-12
Prognostication is critical for accurate diagnosis and tailored treatment in endometrial cancer (EC). We employed radiogenomics to integrate preoperative magnetic resonance imaging (MRI, n = 487 patients) with histologic-, transcriptomic- and molecular biomarkers (n = 550 patients) aiming to identif...
Cancer imagingEndometrial cancer
10.1038/S42003-021-02894-5
ISSN:2399-3642
Repression of LSD1 potentiates homologous recombination-proficient ovarian cancer to PARP inhibitors through down-regulation of BRCA1/2 and RAD51
Lei Tao•Yue Zhou•Xiangyu Pan•Yuan Luo•Jiahao Qiu等 33 人
Nature Communications
2023
•2023/11/16
•Vol.14 No.1 p.1-21
Poly (ADP-ribose) polymerase inhibitors (PARPi) are selectively active in ovarian cancer (OC) with homologous recombination (HR) deficiency (HRD) caused by mutations in BRCA1/2 and other DNA repair pathway members. We sought molecular targeted therapy that induce HRD in HR-proficient cells to induce...
Ovarian cancerTargeted therapies
10.1038/S41467-023-42850-X
ISSN:2041-1723
Citizen-centered, auditable and privacy-preserving population genomics
Dennis Grishin•Jean Louis Raisaro•Juan Ramón Troncoso-Pastoriza•Kamal Obbad•Kevin Quinn等 11 人
Nature Computational Science
2021
•2021/3/25
•Vol.1 No.3 p.192-198
The growing number of health-data breaches, the use of genomic databases for law enforcement purposes and the lack of transparency of personal genomics companies are raising unprecedented privacy concerns. To enable a secure exploration of genomic datasets with controlled and transparent data access...
Computational biology and bioinformaticsData processingGenomicsSoftware
10.1038/S43588-021-00044-9
ISSN:2662-8457
The expanding landscape of ‘oncohistone’ mutations in human cancers
Benjamin A. Nacev•Lijuan Feng•John D. Bagert•Agata E. Lemiesz•JianJiong Gao等 10 人
Nature
2019
•2019/3/20
•Vol.567 No.7749 p.473-478
Mutations in epigenetic pathways are common oncogenic drivers. Histones, the fundamental substrates for chromatin-modifying and remodelling enzymes, are mutated in tumours including gliomas, sarcomas, head and neck cancers, and carcinosarcomas. Classical ‘oncohistone’ mutations occur in the N-termin...
Cancer epigeneticsChromatinEpigenetics
10.1038/S41586-019-1038-1
ISSN:0028-0836
Dissecting tumor transcriptional heterogeneity from single-cell RNA-seq data by generalized binary covariance decomposition
Yusha Liu•Peter Carbonetto•Jason Willwerscheid•Scott A. Oakes•Kay F. Macleod等 6 人
Nature Genetics
2025
•2025/1/2
•00 p.1-11
Profiling tumors with single-cell RNA sequencing has the potential to identify recurrent patterns of transcription variation related to cancer progression, and to produce therapeutically relevant insights. However, strong intertumor heterogeneity can obscure more subtle patterns that are shared acro...
CancerComputational biology and bioinformaticsStatistics
10.1038/S41588-024-01997-Z
ISSN:1061-4036
Estrogen receptor β target gene expression reveals novel repressive functions in aggressive breast cancer
Spyros Tastsoglou•Ilias V. Karagounis•Marios Miliotis•Harika Nagandla•Kristina Diana A. Zambo等 10 人
Npj Breast Cancer
2026
•2026/2/7
•Vol.12 No.1 p.380
Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma, frequently characterized by estrogen receptor alpha (ERα) negativity and limited treatment options. Our previous research showed that the second ER subtype, ERβ, is associated with reduced metastasis in IBC patients and xenogr...
Breast cancerCancerCancer genomics
10.1038/S41523-026-00905-4
ISSN:2374-4677
Pan-cancer computational histopathology reveals mutations, tumor composition and prognosis
Yu Fu•Alexander W. Jung•Ramon Viñas Torne•Santiago Gonzalez•Harald Vöhringer等 10 人
Nature Cancer
2020
•2020/7/27
•Vol.1 No.8 p.800-810
We use deep transfer learning to quantify histopathological patterns across 17,355 hematoxylin and eosin-stained histopathology slide images from 28 cancer types and correlate these with matched genomic, transcriptomic and survival data. This approach accurately classifies cancer types and provides ...
CancerCancer genomicsCancer imagingComputational science
10.1038/S43018-020-0085-8
ISSN:2662-1347
Transcriptional network involving ERG and AR orchestrates Distal-less homeobox-1 mediated prostate cancer progression
Goel Sakshi•Bhatia Vipul•Kundu Sushmita•Biswas Tanay•Carskadon Shannon等 10 人
Nature Communications
2021
•2021/9/7
•Vol.12 No.1 p.1-22
Distal-less homeobox-1 (DLX1) is a well-established non-invasive biomarker for prostate cancer (PCa) diagnosis, however, its mechanistic underpinnings in disease pathobiology are not known. Here, we reveal the oncogenic role of DLX1 and show that abrogating its function leads to reduced tumorigenesi...
Prostate cancer
10.1038/S41467-021-25623-2
ISSN:2041-1723
Multi-omics evaluation of cell lines as models for metastatic prostate cancer
Xueying Liu•Weixing Yu•Xiuyuan Jin•Yugang Wang•Ke Liu
Communications Biology
2026
•2026/3/24
0Cell lines are indispensable tools in prostate cancer research yet their suitability as models for distance metastasis remains incompletely characterized. Here, we conduct a systematic evaluation study using large-scale public multi-omics data. We reveal substantial genomic differences between cell ...
Cancer modelsComputational biology and bioinformaticsMetastasis
10.1038/S42003-026-09914-2
ISSN:2399-3642
Genomic differences of patients with hematologic malignancies in different age groups
Xiaodi Yang•Qian Wang•Yuhua Sun•Ziding Zhang•Stefan Wuchty等 7 人
Communications Biology
2024
•2024/12/6
•Vol.7 No.1 p.1-12
Hematologic malignancies cause significant morbidity/mortality in both children and young adults (CYAs) as well as older adults (OAs). Yet their biological underpinnings remain inadequately understood. Here, we analyzed clinical and genomic disparities between CYAs and OAs in various hematologic mal...
Cancer genomicsHaematological cancerNetwork topology
10.1038/S42003-024-07293-0
ISSN:2399-3642
Copy number amplification of ENSA promotes the progression of triple-negative breast cancer via cholesterol biosynthesis
Chen Yi-Yu•Ge Jing-Yu•Zhu Si-Yuan•Shao Zhi-Ming•Yu Ke-Da
Nature Communications
2022
•2022/2/10
•Vol.13 No.1 p.1-16
Copy number alterations (CNAs) are pivotal genetic events in triple-negative breast cancer (TNBC). Here, our integrated copy number and transcriptome analysis of 302 TNBC patients reveals that gene alpha-endosulfine (ENSA) exhibits recurrent amplification at the 1q21.3 region and is highly expressed...
Breast cancerCancer genomicsCancer metabolism
10.1038/S41467-022-28452-Z
ISSN:2041-1723
AI allows pre-screening of FGFR3 mutational status using routine histology slides of muscle-invasive bladder cancer
Pierre-Antoine Bannier•Charlie Saillard•Philipp Mann•Maxime Touzot•Charles Maussion等 15 人
Nature Communications
2024
•2024/12/30
•Vol.15 No.1 p.1-11
Pathogenic activating mutations in the fibroblast growth factor receptor 3 (FGFR3) drive disease maintenance and progression in urothelial cancer. 10–15% of muscle-invasive and metastatic urothelial cancer (MIBC/mUC) are FGFR3-mutant. Selective targeting of FGFR3 hotspot mutations with tyrosine kina...
Bladder cancerCancer imagingCancer screeningMachine learningTumour biomarkers
10.1038/S41467-024-55331-6
ISSN:2041-1723
S-nitrosylation of IRF7 induced by NOS1 expression in melanoma suppresses anti-tumor immunity
Yuxin Dai•Sisi Zeng•Keyi Li•Jinyan Huang•Minzhu Yang等 18 人
Cell Death & Disease
2026
•2026/1/14
•Vol.17 No.1 p.330
Endogenous nitric oxide (NO) produced by nitric oxide synthases (NOSs) plays an important immunosuppressive role in the tumor microenvironment. In melanoma, NOS1 expression increases with tumor progression and correlates with tumor immune escape through the inhibition of type I interferon (IFN) sign...
Cancer microenvironmentMelanoma
10.1038/S41419-025-08201-Y
ISSN:2041-4889
RNF43 G659fs is an oncogenic colorectal cancer mutation and sensitizes tumor cells to PI3K/mTOR inhibition
Fang Lishan•Ford-Roshon Dane•Russo Max•O’Brien Casey•Xiong Xiaozhe等 15 人
Nature Communications
2022
•2022/6/8
•Vol.13 No.1 p.1-12
The RNF43_p.G659fs mutation occurs frequently in colorectal cancer, but its function remains poorly understood and there are no specific therapies directed against this alteration. In this study, we find that RNF43_p.G659fs promotes cell growth independent of Wnt signaling. We perform a drug repurpo...
Colorectal cancerMolecular biology
10.1038/S41467-022-30794-7
ISSN:2041-1723
ARID1A promotes genomic stability through protecting telomere cohesion
Bo Zhao•Jianhuang Lin•Lijie Rong•Shuai Wu•Zhong Deng等 17 人
Nature Communications
2019
•2019/9/6
•Vol.10 No.1 p.1-13
ARID1A inactivation causes mitotic defects. Paradoxically, cancers with high ARID1A mutation rates typically lack copy number alterations (CNAs). Here, we show that ARID1A inactivation causes defects in telomere cohesion, which selectively eliminates gross chromosome aberrations during mitosis. ARID...
Cancer geneticsOvarian cancer
10.1038/S41467-019-12037-4
ISSN:2041-1723
Peroxisome-driven ether-linked phospholipids biosynthesis is essential for ferroptosis
Weiwei Cui•Dong Liu•Wei Gu•Bo Chu
Cell Death & Differentiation
2021
•2021/3/17
•00 p.1-16
It is well established that ferroptosis is primarily induced by peroxidation of long-chain poly-unsaturated fatty acid (PUFA) through nonenzymatic oxidation by free radicals or enzymatic stimulation of lipoxygenase. Although there is emerging evidence that long-chain saturated fatty acid (SFA) might...
Cancer metabolismPhospholipids
10.1038/S41418-021-00769-0
ISSN:1350-9047
Genomic characterization of the HER2-enriched intrinsic molecular subtype in primary ER-positive HER2-negative breast cancer
Lennart Hohmann•Kristin Sigurjonsdottir•Ana Bosch Campos•Deborah F. Nacer•Srinivas Veerla等 17 人
Nature Communications
2025
•2025/3/5
•Vol.16 No.1 p.1-17
ER-positive/HER2-negative (ERpHER2n) breast cancer classified as PAM50 HER2-enriched (ERpHER2n-HER2E) represents a small high-risk patient subgroup. In this study, we investigate genomic, transcriptomic, and clinical features of ERpHER2n-HER2E breast tumors using two primary ERpHER2n cohorts compris...
Breast cancerCancer geneticsPrognostic markers
10.1038/S41467-025-57419-Z
ISSN:2041-1723
Novel biomarker SARIFA in colorectal cancer: highly prognostic, not genetically driven and histologic indicator of a distinct tumor biology
Nic G. Reitsam•Veselin Grozdanov•Chiara M. L. Löffler•Hannah S. Muti•Bianca Grosser等 7 人
Cancer Gene Therapy
2023
•2023/11/22
•00 p.1-10
SARIFA (Stroma AReactive Invasion Front Areas) has recently emerged as a promising histopathological biomarker for colon and gastric cancer. To elucidate the underlying tumor biology, we assessed SARIFA-status in tissue specimens from The-Cancer-Genome-Atlas (TCGA) cohorts COAD (colonic adenocarcino...
BiomarkersCancer
10.1038/S41417-023-00695-Y
ISSN:0929-1903
Multiscale-omic assessment of EWSR1-NFATc2 fusion positive sarcomas identifies the mTOR pathway as a potential therapeutic target
Nathan D. Seligson•Richard D. Maradiaga•Colin M. Stets•Howard M. Katzenstein•Sherri Z. Millis等 8 人
Npj Precision Oncology
2021
•2021/5/21
•Vol.5 No.1 p.1-11
Sarcomas harboring EWSR1-NFATc2 fusions have historically been categorized and treated as Ewing sarcoma. Emerging evidence suggests unique molecular characteristics and chemotherapy sensitivities in EWSR1-NFATc2 fusion positive sarcomas. Comprehensive genomic profiles of 1024 EWSR1 fusion positive s...
Predictive markersSarcomaTumour biomarkers
10.1038/S41698-021-00177-0
ISSN:2397-768X
FGL2 promotes tumor progression in the CNS by suppressing CD103 + dendritic cell differentiation
Jun Yan•Qingnan Zhao•Konrad Gabrusiewicz•Ling-Yuan Kong•Xueqing Xia等 15 人
Nature Communications
2019
•2019/1/25
•Vol.10 No.1 p.1-15
Few studies implicate immunoregulatory gene expression in tumor cells in arbitrating brain tumor progression. Here we show that fibrinogen-like protein 2 (FGL2) is highly expressed in glioma stem cells and primary glioblastoma (GBM) cells. FGL2 knockout in tumor cells did not affect tumor-cell proli...
CancerCNS cancerTumour immunology
10.1038/S41467-018-08271-X
ISSN:2041-1723
Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis
Teng Gao•Ryan Ptashkin•Kelly L. Bolton•Maria Sirenko•Christopher Fong等 31 人
Nature Communications
2021
•2021/1/12
•Vol.12 No.1 p.1-11
Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have cha...
Cancer genomicsDiagnostic markersEvolutionary geneticsPredictive markersPredictive medicine
10.1038/S41467-020-20565-7
ISSN:2041-1723
Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules
Ignasi Toledano•Fran Supek•Ben Lehner
Nature Genetics
2024
•2024/8/22
•00 p.1-11
Premature termination codons (PTCs) cause ~10–20% of inherited diseases and are a major mechanism of tumor suppressor gene inactivation in cancer. A general strategy to alleviate the effects of PTCs would be to promote translational readthrough. Nonsense suppression by small molecules has proven eff...
Genetics researchGenomicsClinical trial design
10.1038/S41588-024-01878-5
ISSN:1061-4036
The phosphoinositide coincidence detector Phafin2 promotes macropinocytosis by coordinating actin organisation at forming macropinosomes
Schink Kay Oliver•Tan Kia Wee•Spangenberg Hélène•Martorana Domenica•Sneeggen Marte等 10 人
Nature Communications
2021
•2021/11/12
•Vol.12 No.1 p.1-17
Uptake of large volumes of extracellular fluid by actin-dependent macropinocytosis has an important role in infection, immunity and cancer development. A key question is how actin assembly and disassembly are coordinated around macropinosomes to allow them to form and subsequently pass through the d...
EndocytosisEndosomes
10.1038/S41467-021-26775-X
ISSN:2041-1723
Source, co-occurrence, and prognostic value of PTEN mutations or loss in colorectal cancer
Ilya G. Serebriiskii•Valerii A. Pavlov•Grigorii V. Andrianov•Samuel Litwin•Stanley Basickes等 9 人
Npj Genomic Medicine
2023
•2023/11/24
•Vol.8 No.1 p.1-12
Somatic PTEN mutations are common and have driver function in some cancer types. However, in colorectal cancers (CRCs), somatic PTEN-inactivating mutations occur at a low frequency (~8–9%), and whether these mutations are actively selected and promote tumor aggressiveness has been controversial. Ana...
Colorectal cancerMolecular medicine
10.1038/S41525-023-00384-7
ISSN:2056-7944
CDKN2A homozygous deletions and TSC2 somatic mutations in metastatic pancreatic neuroendocrine tumors
Tito Teles Jesus•Lorenzo Ferrando•Lia Rodrigues•Rui Sousa Martins•Luís Cardoso等 9 人
Npj Precision Oncology
2025
•2025/12/5
0Despite improvements in the molecular profiling of pancreatic neuroendocrine tumors (PanNETs), predicting their clinical behavior and response to specific therapies remains challenging. We sought to elucidate the molecular basis underlying the broad phenotypic variations in these neoplasms through a...
Cancer genomicsNeuroendocrine cancerPancreatic cancer
10.1038/S41698-025-01210-2
ISSN:2397-768X
PBRM1 loss defines a nonimmunogenic tumor phenotype associated with checkpoint inhibitor resistance in renal carcinoma
Xian-De Liu•Wen Kong•Christine B. Peterson•Daniel J. McGrail•Anh Hoang等 18 人
Nature Communications
2020
•2020/5/1
•Vol.11 No.1 p.1-14
A non-immunogenic tumor microenvironment (TME) is a significant barrier to immune checkpoint blockade (ICB) response. The impact of Polybromo-1 (PBRM1) on TME and response to ICB in renal cell carcinoma (RCC) remains to be resolved. Here we show that PBRM1/Pbrm1 deficiency reduces the binding of bra...
TranscriptomicsTumour immunology
10.1038/S41467-020-15959-6
ISSN:2041-1723
NAPRT-mediated deamidated NAD biosynthesis enhances colon tissue resiliency and suppresses tumorigenesis
Xiaoyue Wu•Jason G. Williams•Haoyang Liang•Artiom Gruzdev•Joshua Hartsell等 23 人
Nature Communications
2026
•2026/2/10
0Nicotinamide adenine dinucleotide (NAD) is synthesized through both amidated salvage and deamidated pathways. Although NAD-producing enzymes are often overexpressed in cancer cells to meet the high metabolic demands of rapid proliferation and are considered oncogenic, we report that physiological le...
Colon cancerHomeostasisTumour-suppressor proteins
10.1038/S41467-026-68998-W
ISSN:2041-1723
Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation
Vilma Dembitz•Hannah Lawson•Richard Burt•Sirisha Natani•Céline Philippe等 36 人
Leukemia
2024
•2024/8/26
•00 p.1-15
Identification of specific and therapeutically actionable vulnerabilities, ideally present across multiple mutational backgrounds, is needed to improve acute myeloid leukemia (AML) patients’ outcomes. We identify stearoyl-CoA desaturase (SCD), the key enzyme in fatty acid (FA) desaturation, as progn...
Acute myeloid leukaemiaCancer metabolismDrug development
10.1038/S41375-024-02390-9
ISSN:0887-6924
The genotypes and phenotypes of missense mutations in the proline domain of the p53 protein
Hoyos David•Greenbaum Benjamin•Levine Arnold J.
Cell Death & Differentiation
2022
•2022/4/5
•00 p.1-8
The p53 protein is structurally and functionally divided into five domains. The proline-rich domain is localized at amino acids 55–100. 319 missense mutations were identified solely in the proline domain from human cancers. Six hotspot mutations were identified at amino acids 72, 73, 82, 84, 89, and...
Cancer geneticsTumour-suppressor proteins
10.1038/S41418-022-00980-7
ISSN:1350-9047
Super-enhancers orchestrate transcriptional dysregulation and metabolic reprogramming in uveal melanoma
Hui Pan•Weihuan Shao•Huixue Wang•Shengfang Ge•Lingyu Zhang等 8 人
Communications Biology
2025
•2025/6/23
•Vol.8 No.1 p.1-14
Uveal melanoma (UM) is the most common intraocular malignancy in adults and frequently metastasizes. Somatic mutations and chromatin aberrations have been implicated in the pathogenesis of this deadly disease. Despite rapid progress in elucidating the genetic landscape of UM, the epigenetic architec...
Cancer epigeneticsChromatin immunoprecipitationEye cancer
10.1038/S42003-025-08338-8
ISSN:2399-3642
Multi-omics data integration and modeling unravels new mechanisms for pancreatic cancer and improves prognostic prediction
Fraunhoffer Nicolas A.•Abuelafia Analía Meilerman•Bigonnet Martin•Gayet Odile•Roques Julie等 10 人
Npj Precision Oncology
2022
•2022/8/17
•Vol.6 No.1 p.1-16
Pancreatic ductal adenocarcinoma (PDAC), has recently been found to be a heterogeneous disease, although the extension of its diversity remains to be fully understood. Here, we harmonize transcriptomic profiles derived from both PDAC epithelial and microenvironment cells to develop a Master Regulato...
Predictive markersTumour heterogeneity
10.1038/S41698-022-00299-Z
ISSN:2397-768X
Protein phosphatase 2A inactivation induces microsatellite instability, neoantigen production and immune response
Yen Yu-Ting•Chien May•Wu Pei-Yi•Ho Chi-Chang•Ho Chun-Te等 10 人
Nature Communications
2021
•2021/12/15
•Vol.12 No.1 p.1-14
Microsatellite-instable (MSI), a predictive biomarker for immune checkpoint blockade (ICB) response, is caused by mismatch repair deficiency (MMRd) that occurs through genetic or epigenetic silencing of MMR genes. Here, we report a mechanism of MMRd and demonstrate that protein phosphatase 2A (PP2A)...
Cancer immunotherapyColon cancerGene silencingImmunoediting
10.1038/S41467-021-27620-X
ISSN:2041-1723
Breast tumor microenvironment structures are associated with genomic features and clinical outcome
Danenberg Esther•Bardwell Helen•Zanotelli Vito R. T.•Provenzano Elena•Chin Suet-Feung等 13 人
Nature Genetics
2022
•2022/4/18
•00 p.1-10
The functions of the tumor microenvironment (TME) are orchestrated by precise spatial organization of specialized cells, yet little is known about the multicellular structures that form within the TME. Here we systematically mapped TME structures in situ using imaging mass cytometry and multitiered ...
Breast cancerTumour immunology
10.1038/S41588-022-01041-Y
ISSN:1061-4036
Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma
Carmen Oi Ning Leung•Yang Yang•Rainbow Wing Hei Leung•Karl Kam Hei So•Hai Jun Guo等 13 人
Nature Communications
2023
•2023/10/23
•Vol.14 No.1 p.1-20
Increasing evidence has demonstrated that drug resistance can be acquired in cancer cells by kinase rewiring, which is an obstacle for efficient cancer therapy. However, it is technically challenging to measure the expression of protein kinases on large scale due to their dynamic range in human prot...
Cancer stem cellsCancer therapyHepatology
10.1038/S41467-023-42360-W
ISSN:2041-1723
Cancer-associated fibroblasts regulate DNA repair in pancreatic cancer through NDRG1-mediated R-loop processing
Nina Kozlova•Kayla A. Cruz•Antoine A. Ruzette•Hanna M. Doh•Nicholas A. Willis等 36 人
Nature Cell Biology
2026
•2026/4/27
•00 p.1-14
Pancreatic ductal adenocarcinomas (PDACs) are aggressive, stroma-rich tumours. They are unresponsive to treatments, and patients relapse quickly on DNA-damaging chemotherapies. PDAC stroma consists of extracellular matrix proteins (ECM), secreted by cancer-associated fibroblasts (CAFs). Here we show...
Cancer microenvironmentExtracellular matrixPancreatic cancerStalled forks
10.1038/S41556-026-01938-4
ISSN:1465-7392
Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer
Li Zheqi•Spoelstra Nicole S.•Sikora Matthew J.•Sams Sharon B.•Elias Anthony等 8 人
Npj Breast Cancer
2022
•2022/5/10
•Vol.8 No.1 p.1-13
Both TP53 and ESR1 mutations occur frequently in estrogen receptor positive (ER+) metastatic breast cancers (MBC) and their distinct roles in breast cancer tumorigenesis and progression are well appreciated. Recent clinical studies discovered mutual exclusivity between TP53 and ESR1 mutations in met...
Breast cancerEpistasisTranscription
10.1038/S41523-022-00426-W
ISSN:2374-4677
Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results
Palmer Christine D.•Rappaport Amy R.•Davis Matthew J.•Hart Meghan G.•Scallan Ciaran D.等 44 人
Nature Medicine
2022
•2022/8/15
•00 p.1-11
Checkpoint inhibitor (CPI) therapies provide limited benefit to patients with tumors of low immune reactivity. T cell-inducing vaccines hold promise to exert long-lasting disease control in combination with CPI therapy. Safety, tolerability and recommended phase 2 dose (RP2D) of an individualized, h...
Colon cancerColorectal cancerImmunizationRNA vaccinesTranslational research
10.1038/S41591-022-01937-6
ISSN:1078-8956
PARD6A promotes lung adenocarcinoma cell proliferation and invasion through Serpina3
Lanlin Hu•Mingxin Liu•Bo Tang•Xurui Li•Huasheng Xu等 9 人
Cancer Gene Therapy
2024
•2024/9/19
•00 p.1-12
Par6α encoded by PARD6A is a member of the PAR6 family and is reported to promote cancer initiation and progression. PARD6A is frequently upregulated in different types of cancers, but its regulatory role in lung cancer progression is yet to be established. In this study, we analyzed the PARD6A expr...
Cell biologyNon-small-cell lung cancer
10.1038/S41417-024-00829-W
ISSN:0929-1903
Pathogenic germline variants in Chinese pancreatic adenocarcinoma patients
Xiaoyi Yin•Hui Shen•Huan Wang•Qingchen Wang•Shan Zhang等 39 人
Nature Communications
2025
•2025/3/5
•Vol.16 No.1 p.1-20
Putting pancreatic adenocarcinoma (PAAD) screening into perspective for high-risk individuals could significantly reduce cancer morbidity and mortality. Previous studies have profiled somatic mutations in PAAD. In contrast, the prevalence of mutations in PAAD predisposition genes has not been define...
Cancer geneticsCancer genomicsPancreatic cancer
10.1038/S41467-025-57520-3
ISSN:2041-1723
Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation
Elizabeth J. Radford•Hong-Kee Tan•Malin H. L. Andersson•James D. Stephenson•Eugene J. Gardner等 19 人
Nature Communications
2023
•2023/12/6
•Vol.14 No.1 p.1-17
Loss-of-function of DDX3X is a leading cause of neurodevelopmental disorders (NDD) in females. DDX3X is also a somatically mutated cancer driver gene proposed to have tumour promoting and suppressing effects. We perform saturation genome editing of DDX3X, testing in vitro the functional impact of 12...
Cancer geneticsMutagenesisMutationNeurodevelopmental disorders
10.1038/S41467-023-43041-4
ISSN:2041-1723
Lagging strand gap suppression connects BRCA-mediated fork protection to nucleosome assembly through PCNA-dependent CAF-1 recycling
Thakar Tanay•Dhoonmoon Ashna•Straka Joshua•Schleicher Emily M.•Nicolae Claudia M.等 6 人
Nature Communications
2022
•2022/9/9
•Vol.13 No.1 p.1-19
The inability to protect stalled replication forks from nucleolytic degradation drives genome instability and underlies chemosensitivity in BRCA-deficient tumors. An emerging hallmark of BRCA-deficiency is the inability to suppress replication-associated single-stranded DNA (ssDNA) gaps. Here, we re...
DNA damage and repairDNA replication
10.1038/S41467-022-33028-Y
ISSN:2041-1723
Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers
Serebriiskii Ilya G.•Pavlov Valery•Tricarico Rossella•Andrianov Grigorii•Nicolas Emmanuelle等 10 人
Nature Communications
2022
•2022/3/25
•Vol.13 No.1 p.1-17
Loss of expression or activity of the tumor suppressor PTEN acts similarly to an activating mutation in the oncogene PIK3CA in elevating intracellular levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), inducing signaling by AKT and other pro-tumorigenic signaling proteins. Here, we analyze...
Cancer geneticsCancer genomicsColorectal cancerTumour-suppressor proteins
10.1038/S41467-022-29227-2
ISSN:2041-1723
Spatiotemporal multi-omics analysis uncovers NAD-dependent immunosuppressive niche triggering early gastric cancer
Pingting Gao•Chunman Zuo•Wei Yuan•Jiabin Cai•Xiaoqiang Chai等 16 人
Signal Transduction And Targeted Therapy
2025
•2025/9/22
•Vol.10 No.1 p.1-19
Understanding the cellular origins and early evolutionary dynamics that drive the initiation of carcinogenesis is critical to advancing early detection and prevention strategies. By characterizing key molecular, cellular and niche events at the precancerous tipping point of early gastric cancer (EGC...
Gastrointestinal cancerOncogenes
10.1038/S41392-025-02390-W
ISSN:2059-3635
Signaling of MK2 sustains robust AP1 activity for triple negative breast cancer tumorigenesis through direct phosphorylation of JAB1
Haoming Chen•Ravi Padia•Tao Li•Yue Li•Bin Li等 7 人
Npj Breast Cancer
2021
•2021/7/9
•Vol.7 No.1 p.1-13
Triple negative breast cancer (TNBC) cells are generally more invasive than estrogen receptor-positive (ER + ) breast cancer cells. Consistent with the importance of activator protein 1 (AP1) transcription factors in invasion, AP1 activity is much higher in TNBC lines than ER + lines. In TNBC cells,...
Breast cancerCell signalling
10.1038/S41523-021-00300-1
ISSN:2374-4677
Enhancer and metabolic rewiring by KMT2C–COMPASS or KMT2D–COMPASS family loss in cancer creates druggable vulnerabilities
Zibo Zhao•Ali Shilatifard
Nature Reviews Cancer
2026
•2026/4/24
•00 p.1-15
Many epigenetic regulatory factors are targets of the somatic mutations found in patient tumours. Amongst the family of epigenetic regulatory complexes known as Complex of Proteins Associated with Set1 (COMPASS), the enhancer regulators histone-lysine N-methyltransferase 2C (KMT2C)–COMPASS and KMT2D...
BiochemistryCancerEpigenetics
10.1038/S41568-026-00919-X
ISSN:1474-175X
PTENα functions as an immune suppressor and promotes immune resistance in PTEN-mutant cancer
Sun Yizhe•Lu Dan•Yin Yue•Song Jia•Liu Yang等 15 人
Nature Communications
2021
•2021/8/26
•Vol.12 No.1 p.1-17
PTEN is frequently mutated in human cancers and PTEN mutants promote tumor progression and metastasis. PTEN mutations have been implicated in immune regulation, however, the underlying mechanism is largely unknown. Here, we report that PTENα, the isoform of PTEN, remains active in cancer bearing sto...
Tumour immunology
10.1038/S41467-021-25417-6
ISSN:2041-1723
Phosphoglycerate dehydrogenase stabilizes protein kinase C delta type mRNA to promote hepatocellular carcinoma progression
Bin Cheng•Pai Peng•Shi Chen•Rui Liu•Xiaosong Li等 10 人
Signal Transduction And Targeted Therapy
2025
•2025/7/18
•Vol.10 No.1 p.1-15
Metabolic reprogramming not only reshapes cellular bioenergetics but also profoundly influences RNA metabolism through metabolite signaling and the RNA-binding activities of metabolic enzymes. Emerging evidence highlights that certain metabolic enzymes act as RNA-binding proteins (RBPs) to regulate ...
Cell biologyMolecular biology
10.1038/S41392-025-02304-W
ISSN:2059-3635
A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells
Maryam Ghaderi Najafabadi•G. Kenneth Gray•Li Ren Kong•Komal Gupta•David Perera等 9 人
Nature Communications
2023
•2023/8/25
•Vol.14 No.1 p.1-17
Germline BRCA2 mutation carriers frequently develop luminal-like breast cancers, but it remains unclear how BRCA2 mutations affect mammary epithelial subpopulations. Here, we report that monoallelic Brca2mut/WT mammary organoids subjected to replication stress activate a transcriptional response tha...
Breast cancerDisease modelDNA damage response
10.1038/S41467-023-40956-W
ISSN:2041-1723
Prostaglandin E2-driven dedifferentiation of Schwann cells leads to perineural invasion in pancreatic ductal adenocarcinoma
Ling Wang•Qicai Liu•Zhibo Zhang•Shizhong Yang•Juan Tang等 12 人
Signal Transduction And Targeted Therapy
2026
•2026/4/7
•Vol.11 No.1 p.1220
Perineural invasion (PNI), a prominent pathological feature of pancreatic ductal adenocarcinoma (PDAC), is closely associated with poor prognosis. Clarifying its mechanism is therefore critical for developing new therapies. Recent research has focused on the crosstalk between tumors and Schwann cell...
Gastrointestinal cancer
10.1038/S41392-026-02648-X
ISSN:2059-3635
Decoding the functional impact of the cancer genome through protein–protein interactions
Haian Fu•Xiulei Mo•Andrey A. Ivanov
Nature Reviews Cancer
2025
•2025/1/14
•00 p.1-20
Acquisition of genomic mutations enables cancer cells to gain fitness advantages under selective pressure and, ultimately, leads to oncogenic transformation. Interestingly, driver mutations, even within the same gene, can yield distinct phenotypes and clinical outcomes, necessitating a mutation-focu...
Cancer genomicsOncogenesTarget identificationTumour-suppressor proteins
10.1038/S41568-024-00784-6
ISSN:1474-175X
Dissection of PD-L1 promoter reveals differential transcriptional regulation of PD-L1 in VHL mutant clear cell renal cell carcinoma
Kong Su-Kang•Kim Byung Soo•Lim Hyangsoon•Kim Hyun Ji•Kim Young-Sik
Laboratory Investigation
2021
•2021/11/17
•00 p.1-11
Programmed death-ligand 1 (PD-L1) is constitutively expressed by hypoxia-inducible factor 2α (HIF2α). It can be induced by interferon gamma (IFNγ) signaling in clear cell renal cell carcinoma (ccRCC). Clinical trials of metastatic ccRCCs have suggested that a canonical IFNγ signature is a better bio...
Immune evasionRenal cell carcinoma
10.1038/S41374-021-00703-5
ISSN:0023-6837
SMAD4 induces opposite effects on metastatic growth from pancreatic tumors depending on the organ of residence
Kaloyan M. Tsanov•Francisco M. Barriga•Yu-Jui Ho•Direna Alonso-Curbelo•Geulah Livshits等 23 人
Nature Cancer
2025
•2025/9/25
•00 p.1-18
The role of driver gene mutations in sustaining tumor growth at metastatic sites is poorly understood. SMAD4 inactivation is a paradigm of such mutations and a hallmark of pancreatic ductal adenocarcinoma (PDAC). To determine whether metastatic tumors are dependent on SMAD4 inactivation, we develope...
CancerCancer epigeneticsMetastasisPancreatic cancer
10.1038/S43018-025-01047-5
ISSN:2662-1347
Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine
Yasaman Barekatain•Jeffrey J. Ackroyd•Victoria C. Yan•Sunada Khadka•Lin Wang等 21 人
Nature Communications
2021
•2021/7/9
•Vol.12 No.1 p.1-13
Homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP’s substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protei...
Cancer metabolismCNS cancer
10.1038/S41467-021-24240-3
ISSN:2041-1723
AXL activates YAP through the EGFR–LATS1/2 axis and confers resistance to EGFR-targeted drugs in head and neck squamous cell carcinoma
Kento Okamoto•Toshinori Ando•Hiroki Izumi•Susumu S. Kobayashi•Tomoaki Shintani等 9 人
Oncogene
2023
•2023/8/17
•00 p.1-9
The Hippo signaling pathway and its downstream effector YAP play a central role in cell proliferation. Dysregulation of the Hippo pathway triggers YAP hyperactivation, thereby inducing head and neck squamous cell carcinoma (HNSCC). Recently, we reported that EGFR promotes tyrosine phosphorylation of...
Non-small-cell lung cancerOral cancer
10.1038/S41388-023-02810-7
ISSN:0950-9232
MIF is a 3’ flap nuclease that facilitates DNA replication and promotes tumor growth
Yijie Wang•Yan Chen•Chenliang Wang•Mingming Yang•Yanan Wang等 16 人
Nature Communications
2021
•2021/5/19
•Vol.12 No.1 p.1-17
How cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3’ flap nuclease that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the ...
DNA damage and repairDNA synthesis
10.1038/S41467-021-23264-Z
ISSN:2041-1723
TRIM28-dependent developmental heterogeneity determines cancer susceptibility through distinct epigenetic states
Ilaria Panzeri•Luca Fagnocchi•Stefanos Apostle•Megan Tompkins•Emily Wolfrum等 17 人
Nature Cancer
2025
•2025/1/24
•Vol.6 No.2 p.385-403
Mutations in cancer risk genes increase susceptibility, but not all carriers develop cancer. Indeed, while DNA mutations are necessary drivers of cancer, only a small subset of mutated cells go on to cause the disease. To date, the mechanisms underlying individual cancer susceptibility remain unclea...
CancerCancer epigeneticsDNA methylation
10.1038/S43018-024-00900-3
ISSN:2662-1347
cGAS-STING pathway expression correlates with genomic instability and immune cell infiltration in breast cancer
Mengting Chen•Shibo Yu•Tineke van der Sluis•Mieke C. Zwager•Carolien P. Schröder等 7 人
Npj Breast Cancer
2024
•2024/1/2
•Vol.10 No.1 p.1-13
Genomic instability, as caused by oncogene-induced replication stress, can lead to the activation of inflammatory signaling, involving the cGAS-STING and JAK-STAT pathways. Inflammatory signaling has been associated with pro-tumorigenic features, but also with favorable response to treatment, includ...
Breast cancerTumour heterogeneity
10.1038/S41523-023-00609-Z
ISSN:2374-4677
Parallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT
Paul Indranil•Bolzan Dante•Youssef Ahmed•Gagnon Keith A.•Hook Heather等 22 人
Nature Communications
2023
•2023/2/8
•Vol.14 No.1 p.1-23
A proper understanding of disease etiology will require longitudinal systems-scale reconstruction of the multitiered architecture of eukaryotic signaling. Here we combine state-of-the-art data acquisition platforms and bioinformatics tools to devise PAMAF, a workflow that simultaneously examines twe...
Breast cancerCancer genomicsEpithelial–mesenchymal transitionProteome informaticsTime series
10.1038/S41467-023-36122-X
ISSN:2041-1723
Evolutionary signatures of human cancers revealed via genomic analysis of over 35,000 patients
Diletta Fontana•Ilaria Crespiatico•Valentina Crippa•Federica Malighetti•Matteo Villa等 14 人
Nature Communications
2023
•2023/9/25
•Vol.14 No.1 p.1-18
Recurring sequences of genomic alterations occurring across patients can highlight repeated evolutionary processes with significant implications for predicting cancer progression. Leveraging the ever-increasing availability of cancer omics data, here we unveil cancer’s evolutionary signatures tied t...
Cancer geneticsCancer genomicsComputational biology and bioinformatics
10.1038/S41467-023-41670-3
ISSN:2041-1723
Genetic mutation and biological pathway prediction based on whole slide images in breast carcinoma using deep learning
Qu Hui•Zhou Mu•Yan Zhennan•Wang He•Rustgi Vinod K.等 8 人
Npj Precision Oncology
2021
•2021/9/23
•Vol.5 No.1 p.1-11
Breast carcinoma is the most common cancer among women worldwide that consists of a heterogeneous group of subtype diseases. The whole-slide images (WSIs) can capture the cell-level heterogeneity, and are routinely used for cancer diagnosis by pathologists. However, key driver genetic mutations rela...
Breast cancerCancer genomicsCancer imaging
10.1038/S41698-021-00225-9
ISSN:2397-768X
RASH3D19 mediates RAS activation through a positive feedback loop in KRAS-mutant cancer
Warapen Treekitkarnmongkol•Hiroshi Katayama•Deivendran Sankaran•Mei-Chee Tai•Sanchita Rauth等 20 人
Nature Cell Biology
2025
•2025/12/1
•00 p.1-10
Therapeutic targeting of mutant KRAS pathways driving cancers is being actively investigated to identify feedback mechanisms responsible for the development of adaptive resistance to mutant KRAS inhibitors undergoing clinical trials. Here we report RASH3D19 as a mediator of RAS pathway activation th...
Cancer therapeutic resistanceOncogenesTargeted therapies
10.1038/S41556-025-01816-5
ISSN:1465-7392
Transcriptional reprogramming triggered by neonatal UV radiation or Lkb1 loss prevents BRAFV600E-induced growth arrest in melanocytes
Kimberley McGrail•Paula Granado-Martínez•Roberto Orsenigo•Ginevra Caratù•Paula Nieto等 11 人
Oncogene
2025
•2025/3/8
•00 p.1-17
The mechanisms behind UVB-initiated, neonatal-specific melanoma linked to BRAFV600E are not well understood, particularly regarding its role in growth arrest. We found that, beyond mutations, neonatal UV irradiation or Lkb1 loss promotes a cell-autonomous transcriptional reprogramming that prevents ...
Cell divisionGene expressionMechanisms of diseaseMelanoma
10.1038/S41388-025-03339-7
ISSN:0950-9232
Tumor cell-intrinsic PD-1 regulates chemotherapy resistance in colorectal cancer cells by activating downstream MAPK signaling
Ho Kit Mok•Sophie Sneddon•Jianhua Ren•Donald T. T. Yapp•Isabella T. Tai
Bjc Reports
2025
•2025/11/19
•Vol.3 No.1 p.820
Colorectal cancer (CRC) remains a significant clinical challenge. Immunotherapy against programmed cell death 1 protein (PD-1) in CRC has limited success. Intriguingly, CRC cells express PD-1 (ciPD-1) intrinsically, and we report here its function with respect to chemotherapy. We evaluated the assoc...
Cancer ResearchOncology
10.1038/S44276-025-00185-8
ISSN:2731-9377
The m6A reader IGF2BP3 promotes acute myeloid leukemia progression by enhancing RCC2 stability
Zhang Nan•Shen Yan•Li Huan•Chen Ying•Zhang Ping等 7 人
Experimental & Molecular Medicine
2022
•2022/2/25
•Vol.54 No.2 p.194-205
N6-methyladenosine (m6A) is the most abundant posttranscriptional modification of mRNA in eukaryotes. Recent evidence suggests that dysregulated m6A-associated proteins and m6A modifications play a pivotal role in the initiation and progression of diseases such as cancer. Here, we identified that IG...
EpigeneticsMyeloma
10.1038/S12276-022-00735-X
ISSN:1226-3613
Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures
Georgeson Peter•Harrison Tabitha A.•Pope Bernard J.•Zaidi Syed H.•Qu Conghui等 52 人
Nature Communications
2022
•2022/6/6
•Vol.13 No.1 p.1-12
Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncert...
Cancer geneticsCancer genomicsColorectal cancerStatistical methods
10.1038/S41467-022-30916-1
ISSN:2041-1723
Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy
Álvarez-Varela Adrián•Novellasdemunt Laura•Barriga Francisco M.•Hernando-Momblona Xavier•Cañellas-Socias Adrià等 23 人
Nature Cancer
2022
•2022/6/30
•00 p.1-19
Colorectal cancer (CRC) patient-derived organoids predict responses to chemotherapy. Here we used them to investigate relapse after treatment. Patient-derived organoids expand from highly proliferative LGR5+ tumor cells; however, we discovered that lack of optimal growth conditions specifies a laten...
Cancer stem cellsCancer therapeutic resistanceChemotherapyColon cancer
10.1038/S43018-022-00402-0
ISSN:2662-1347
Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling
Hao Huang•Jianyang Hu•Alishba Maryam•Qinghua Huang•Yuchen Zhang等 17 人
Nature Communications
2021
•2021/4/14
•Vol.12 No.1 p.1-16
Breast cancer is a heterogeneous disease, affecting over 3.5 million women worldwide, yet the functional role of cis-regulatory elements including super-enhancers in different breast cancer subtypes remains poorly characterized. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast...
Breast cancerGene regulatory networks
10.1038/S41467-021-22445-0
ISSN:2041-1723
Temporal tissue dynamics from a spatial snapshot
Jonathan Somer•Shie Mannor•Uri Alon
Nature
2026
•2026/1/21
•Vol.650 No.8101 p.490-499
Physiological and pathological processes such as inflammation and cancer emerge from interactions between cells over time1. However, methods to follow cell populations over time within the native context of a human tissue are lacking because a biopsy offers only a single snapshot. Here we present on...
Cancer modelsComputational biophysicsDynamical systemsMulticellular systemsStochastic modelling
10.1038/S41586-025-09876-1
ISSN:0028-0836
Interplay between DNA damage repair and apoptosis shapes cancer evolution through aneuploidy and microsatellite instability
Noam Auslander•Yuri I. Wolf•Eugene V. Koonin
Nature Communications
2020
•2020/3/6
•Vol.11 No.1 p.1-11
Driver mutations and chromosomal aneuploidy are major determinants of tumorigenesis that exhibit complex relationships. Here, we identify associations between driver mutations and chromosomal aberrations that define two tumor clusters, with distinct regimes of tumor evolution underpinned by unique s...
Cancer genomicsGenome informatics
10.1038/S41467-020-15094-2
ISSN:2041-1723
UBR5 targets tumor suppressor CDC73 proteolytically to promote aggressive breast cancer
Xiang Gang•Wang Shuxuan•Chen Ling•Song Mei•Song Xiaoxu等 9 人
Cell Death & Disease
2022
•2022/5/12
•Vol.13 No.5 p.1-14
UBR5, a HECT-domain E3 ubiquitin ligase, is an attractive therapeutic target for aggressive breast cancers. Defining the substrates of UBR5 is crucial for scientific understanding and clinical intervention. Here, we demonstrate that CDC73, a component of the RNA polymerase II-associated factor 1 com...
Breast cancerTumour-suppressor proteinsUbiquitylation
10.1038/S41419-022-04914-6
ISSN:2041-4889
Pervasive structural heterogeneity rewires glioblastoma chromosomes to sustain patient-specific transcriptional programs
Ting Xie•Adi Danieli-Mackay•Mariachiara Buccarelli•Mariano Barbieri•Ioanna Papadionysiou等 17 人
Nature Communications
2024
•2024/5/9
•Vol.15 No.1 p.1-16
Glioblastoma multiforme (GBM) encompasses brain malignancies marked by phenotypic and transcriptional heterogeneity thought to render these tumors aggressive, resistant to therapy, and inevitably recurrent. However, little is known about how the spatial organization of GBM genomes underlies this het...
Cancer genomicsCancer stem cellsEpigenomics
10.1038/S41467-024-48053-2
ISSN:2041-1723
The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences
Jia-Wern Pan•Muhammad Mamduh Ahmad Zabidi•Pei-Sze Ng•Mei-Yee Meng•Siti Norhidayu Hasan等 13 人
Nature Communications
2020
•2020/12/22
•Vol.11 No.1 p.1-12
Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 56...
Breast cancerCancer genomics
10.1038/S41467-020-20173-5
ISSN:2041-1723
Nuclear speckles regulate functional programs in cancer
Katherine A. Alexander•Ruofan Yu•Nicolas Skuli•Nathan J. Coffey•Son Nguyen等 18 人
Nature Cell Biology
2025
•2025/1/2
•00 p.1-14
Nuclear speckles are dynamic nuclear bodies characterized by high concentrations of factors involved in RNA production. Although the contents of speckles suggest multifaceted roles in gene regulation, their biological functions are unclear. Here we investigate speckle variation in human cancer, find...
OncogenesNuclear speckles
10.1038/S41556-024-01570-0
ISSN:1465-7392
A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma
Akimasa Hayashi•Jun Fan•Ruoyao Chen•Yu-jui Ho•Alvin P. Makohon-Moore等 29 人
Nature Cancer
2020
•2020/1/13
•Vol.1 No.1 p.59-74
Pancreatic cancer expression profiles largely reflect a classical or basal-like phenotype. The extent to which these profiles vary within a patient is unknown. We integrated evolutionary analysis and expression profiling in multiregion-sampled metastatic pancreatic cancers, finding that squamous fea...
Cancer genomicsPancreatic cancerTumour heterogeneity
10.1038/S43018-019-0010-1
ISSN:2662-1347
The NUCKS1-SKP2-p21/p27 axis controls S phase entry
Hume Samuel•Grou Claudia P.•Lascaux Pauline•D’Angiolella Vincenzo•Legrand Arnaud J.等 7 人
Nature Communications
2021
•2021/11/29
•Vol.12 No.1 p.1-14
Efficient entry into S phase of the cell cycle is necessary for embryonic development and tissue homoeostasis. However, unscheduled S phase entry triggers DNA damage and promotes oncogenesis, underlining the requirement for strict control. Here, we identify the NUCKS1-SKP2-p21/p27 axis as a checkpoi...
BiochemistryCell-cycle exitCheckpointsGene expression analysisUbiquitin ligases
10.1038/S41467-021-27124-8
ISSN:2041-1723
Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer
Xinjian Liu•Xuhui Bao•Mengjie Hu•Hanman Chang•Meng Jiao等 10 人
Nature
2020
•2020/11/11
•Vol.588 No.7839 p.693-698
Despite its success in achieving the long-term survival of 10–30% of treated individuals, immune therapy is still ineffective for most patients with cancer1,2. Many efforts are therefore underway to identify new approaches that enhance such immune ‘checkpoint’ therapy3–5 (so called because its aim i...
Cancer immunotherapyCancer microenvironmentCancer therapeutic resistance
10.1038/S41586-020-2911-7
ISSN:0028-0836
KRAS regulation by small non-coding RNAs and SNARE proteins
Yonglu Che•Zurab Siprashvili•Joanna R. Kovalski•Tiffany Jiang•Glenn Wozniak等 7 人
Nature Communications
2019
•2019/11/11
•Vol.10 No.1 p.1-15
KRAS receives and relays signals at the plasma membrane (PM) where it transmits extracellular growth factor signals to downstream effectors. SNORD50A/B were recently found to bind KRAS and inhibit its tumorigenic action by unknown mechanisms. KRAS proximity protein labeling was therefore undertaken ...
CancerGenetics
10.1038/S41467-019-13106-4
ISSN:2041-1723
Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity
Cindy Yang S. Y.•Lien Scott C.•Wang Ben X.•Clouthier Derek L.•Hanna Youstina等 27 人
Nature Communications
2021
•2021/8/26
•Vol.12 No.1 p.1-15
Serial circulating tumor DNA (ctDNA) monitoring is emerging as a non-invasive strategy to predict and monitor immune checkpoint blockade (ICB) therapeutic efficacy across cancer types. Yet, limited data exist to show the relationship between ctDNA dynamics and tumor genome and immune microenvironmen...
Cancer genomicsImmunotherapyTumour biomarkers
10.1038/S41467-021-25432-7
ISSN:2041-1723
FSP1 confers ferroptosis resistance in KEAP1 mutant non-small cell lung carcinoma in NRF2-dependent and -independent manner
Jong Woo Kim•Min-Ju Kim•Tae-Hee Han•Ji-Yoon Lee•Sangok Kim等 15 人
Cell Death & Disease
2023
•2023/8/26
•Vol.14 No.8 p.1-11
Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genom...
Cell deathNon-small-cell lung cancer
10.1038/S41419-023-06070-X
ISSN:2041-4889
Proteomics-derived basal biomarker DNA-PKcs is associated with intrinsic subtype and long-term clinical outcomes in breast cancer
Asleh Karama•Riaz Nazia•Cheng Angela S.•Gao Dongxia•Leung Samuel C. Y.等 7 人
Npj Breast Cancer
2021
•2021/9/9
•Vol.7 No.1 p.1-13
Precise biomarkers are needed to guide better diagnostics and therapeutics for basal-like breast cancer, for which DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has been recently reported by the Clinical Proteomic Tumor Analysis Consortium as the most specific biomarker. We evaluated DNA...
Breast cancerPrognostic markers
10.1038/S41523-021-00320-X
ISSN:2374-4677
ARID1A loss induces polymorphonuclear myeloid-derived suppressor cell chemotaxis and promotes prostate cancer progression
Li Ni•Liu Qiuli•Han Ying•Pei Siyu•Cheng Bisheng等 23 人
Nature Communications
2022
•2022/11/26
•Vol.13 No.1 p.1-20
Chronic inflammation and an immunosuppressive microenvironment promote prostate cancer (PCa) progression and diminish the response to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here, we show that ARID1A, a subunit ...
Cancer microenvironmentEpigeneticsProstate cancer
10.1038/S41467-022-34871-9
ISSN:2041-1723
Targeting the DYRK1A kinase prevents cancer progression and metastasis and promotes cancer cells response to G1/S targeting chemotherapy drugs
Amina Jamal Laham•Raafat El-Awady•Maha Saber Ayad•Ni Wang•Gang Yan等 8 人
Npj Precision Oncology
2024
•2024/6/5
•Vol.8 No.1 p.1-14
Metastatic cancer remains incurable as patients eventually loose sensitivity to targeted therapies and chemotherapies, further leading to poor clinical outcome. Thus, there is a clear medical gap and urgent need to develop efficient and improved targeted therapies for cancer patients. In this study,...
Breast cancerColon cancer
10.1038/S41698-024-00614-W
ISSN:2397-768X
CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer
Chunge Zhong•Wen-Jie Jiang•Yingjia Yao•Zexu Li•You Li等 35 人
Nature Communications
2024
•2024/6/29
•Vol.15 No.1 p.1-21
Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. C...
Cancer geneticsCancer genomicsMechanism of action
10.1038/S41467-024-49673-4
ISSN:2041-1723
The comparison of cancer gene mutation frequencies in Chinese and U.S. patient populations
Ma Fayang•Laster Kyle•Dong Zigang
Nature Communications
2022
•2022/9/26
•Vol.13 No.1 p.1-12
Knowing the mutation frequency of cancer genes in China is crucial for reducing the global health burden. We integrate the tumor epidemiological statistics with cancer gene mutation rates identified in 11,948 cancer patients to determine their weighted proportions within a Chinese cancer patient coh...
Cancer epidemiologyCancer geneticsOncogenes
10.1038/S41467-022-33351-4
ISSN:2041-1723
Crosstalk between SUMOylation and ubiquitylation controls DNA end resection by maintaining MRE11 homeostasis on chromatin
Zhang Tao•Yang Han•Zhou Zenan•Bai Yongtai•Wang Jiadong等 6 人
Nature Communications
2022
•2022/9/1
•Vol.13 No.1 p.1-17
DNA end resection is delicately regulated through various types of post-translational modifications to initiate homologous recombination, but the involvement of SUMOylation in this process remains incompletely understood. Here, we show that MRE11 requires SUMOylation to shield it from ubiquitin-medi...
Double-strand DNA breaksHomologous recombination
10.1038/S41467-022-32920-X
ISSN:2041-1723
The immune checkpoint B7x expands tumor-infiltrating Tregs and promotes resistance to anti-CTLA-4 therapy
John Peter•Pulanco Marc C.•Galbo Phillip M.•Wei Yao•Ohaegbulam Kim C.等 7 人
Nature Communications
2022
•2022/5/6
•Vol.13 No.1 p.1-15
Immune checkpoint molecules play critical roles in regulating the anti-tumor immune response, and tumor cells often exploit these pathways to inhibit and evade the immune system. The B7-family immune checkpoint B7x is widely expressed in a broad variety of cancer types, and is generally associated w...
Tumour immunology
10.1038/S41467-022-30143-8
ISSN:2041-1723
Genome-wide CRISPR screen identifies PRC2 and KMT2D-COMPASS as regulators of distinct EMT trajectories that contribute differentially to metastasis
Zhang Yun•Donaher Joana Liu•Das Sunny•Li Xin•Reinhardt Ferenc等 21 人
Nature Cell Biology
2022
•2022/4/11
•00 p.1-11
Epithelial–mesenchymal transition (EMT) programs operate within carcinoma cells, where they generate phenotypes associated with malignant progression. In their various manifestations, EMT programs enable epithelial cells to enter into a series of intermediate states arrayed along the E–M phenotypic ...
Breast cancerChromatin remodellingEpithelial–mesenchymal transitionMetastasis
10.1038/S41556-022-00877-0
ISSN:1465-7392
KMT2C deficiency promotes small cell lung cancer metastasis through DNMT3A-mediated epigenetic reprogramming
Na Feifei•Pan Xiangyu•Chen Jingyao•Chen Xuelan•Wang Manli等 47 人
Nature Cancer
2022
•2022/4/21
•00 p.1-15
Small cell lung cancer (SCLC) is notorious for its early and frequent metastases, which contribute to it as a recalcitrant malignancy. To understand the molecular mechanisms underlying SCLC metastasis, we generated SCLC mouse models with orthotopically transplanted genome-edited lung organoids and p...
CancerEpigeneticsMetastasisSmall-cell lung cancer
10.1038/S43018-022-00361-6
ISSN:2662-1347
TCR-engineered T cells targeting a shared β-catenin mutation eradicate solid tumors
Maria Stadheim Eggebø•Julia Heinzelbecker•Heyilimu Palashati•Nicholas Chandler•Trung The Tran等 15 人
Nature Immunology
2025
•2025/8/27
•00 p.1-11
HLA-bound peptides encoded by recurrent driver mutations are candidate targets for T cell-directed immunotherapy. Here we identify two neopeptides encoded by the CTNNB1S37F mutation presented on the frequent HLA-A*02:01 and HLA-A*24:02 molecules in cell lines naturally expressing the mutation and HL...
Applied immunologyCancer immunotherapy
10.1038/S41590-025-02252-1
ISSN:1529-2908
Midkine activation of CD8 + T cells establishes a neuron–immune–cancer axis responsible for low-grade glioma growth
Xiaofan Guo•Yuan Pan•Min Xiong•Shilpa Sanapala•Corina Anastasaki等 8 人
Nature Communications
2020
•2020/5/1
•Vol.11 No.1 p.1-15
Brain tumors (gliomas) are heterogeneous cellular ecosystems, where non-neoplastic monocytic cells have emerged as key regulators of tumor maintenance and progression. However, relative to macrophages/microglia, comparatively less is known about the roles of neurons and T cells in glioma pathobiolog...
CNS cancerTumour immunology
10.1038/S41467-020-15770-3
ISSN:2041-1723
Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer
Martins Filipe Correia•Couturier Dominique-Laurent•de Santiago Ines•Sauer Carolin Margarethe•Vias Maria等 33 人
Nature Communications
2022
•2022/10/26
•Vol.13 No.1 p.1-14
Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and ...
CancerCancer genomicsCancer modelsOvarian cancerTargeted therapies
10.1038/S41467-022-33870-0
ISSN:2041-1723
Discovery of putative tumor suppressors from CRISPR screens reveals rewired lipid metabolism in acute myeloid leukemia cells
Lenoir W. Frank•Morgado Micaela•DeWeirdt Peter C.•McLaughlin Megan•Griffith Audrey L.等 14 人
Nature Communications
2021
•2021/11/11
•Vol.12 No.1 p.1-15
CRISPR knockout fitness screens in cancer cell lines reveal many genes whose loss of function causes cell death or loss of fitness or, more rarely, the opposite phenotype of faster proliferation. Here we demonstrate a systematic approach to identify these proliferation suppressors, which are highly ...
Acute myeloid leukaemiaCancer metabolismGenetic interactionHigh-throughput screening
10.1038/S41467-021-26867-8
ISSN:2041-1723
Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis
Yu Muta•Juan F. Linares•Anxo Martinez-Ordoñez•Angeles Duran•Tania Cid-Diaz等 26 人
Nature Communications
2023
•2023/12/13
•Vol.14 No.1 p.1-20
The metabolic and signaling pathways regulating aggressive mesenchymal colorectal cancer (CRC) initiation and progression through the serrated route are largely unknown. Although relatively well characterized as BRAF mutant cancers, their poor response to current targeted therapy, difficult preneopl...
Cancer metabolismColon cancer
10.1038/S41467-023-43690-5
ISSN:2041-1723
Engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts to potentiate therapy of pancreatic cancer
Pengcheng Zhou•Xuanlong Du•Weilu Jia•Kun Feng•Yewei Zhang
Signal Transduction And Targeted Therapy
2024
•2024/6/24
•Vol.9 No.1 p.1-20
Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for it. The tumor microenvironment (TME) in pancreatic cancer, distinguished by fibrosis and the existence of cancer-associated fibroblasts (CAFs), exerts a pivotal i...
Cancer microenvironmentDrug deliveryNanobiotechnology
10.1038/S41392-024-01872-7
ISSN:2059-3635
Distinction of lymphoid and myeloid clonal hematopoiesis
Niroula Abhishek•Sekar Aswin•Murakami Mark A.•Trinder Mark•Agrawal Mridul等 15 人
Nature Medicine
2021
•2021/10/18
•00 p.1-7
Clonal hematopoiesis (CH) results from somatic genomic alterations that drive clonal expansion of blood cells. Somatic gene mutations associated with hematologic malignancies detected in hematopoietic cells of healthy individuals, referred to as CH of indeterminate potential (CHIP), have been associ...
Genetics researchHaematological cancer
10.1038/S41591-021-01521-4
ISSN:1078-8956
Self-supervised attention-based deep learning for pan-cancer mutation prediction from histopathology
Saldanha Oliver Lester•Loeffler Chiara M. L.•Niehues Jan Moritz•van Treeck Marko•Seraphin Tobias P.等 11 人
Npj Precision Oncology
2023
•2023/3/28
•Vol.7 No.1 p.1-5
The histopathological phenotype of tumors reflects the underlying genetic makeup. Deep learning can predict genetic alterations from pathology slides, but it is unclear how well these predictions generalize to external datasets. We performed a systematic study on Deep-Learning-based prediction of ge...
Computational biology and bioinformaticsDiagnostic markersMathematics and computing
10.1038/S41698-023-00365-0
ISSN:2397-768X
Integrated analysis of patient samples identifies biomarkers for venetoclax efficacy and combination strategies in acute myeloid leukemia
Haijiao Zhang•Yusuke Nakauchi•Thomas Köhnke•Melissa Stafford•Daniel Bottomly等 10 人
Nature Cancer
2020
•2020/8/18
•Vol.1 No.8 p.826-839
Deregulation of the BCL2 gene family plays an important role in the pathogenesis of acute myeloid leukemia (AML). A BCL2 inhibitor, venetoclax, has received approval from the US Food and Drug Administration for the treatment of AML. However, upfront and acquired drug resistance ensues, in part due t...
CancerCancer therapeutic resistanceLeukaemiaPredictive markers
10.1038/S43018-020-0103-X
ISSN:2662-1347
A dependency map enhanced with next-generation 3D cancer models
James V. Neiswender•Samuel Maffa•Lisa Brenan•Dina ElHarouni•Yejie Yun等 69 人
Nature
2026
•2026/8/5
•00 p.1-11
Despite advances in precision oncology, effective personalized treatments are still lacking for most patients with cancer1. The Cancer Dependency Map (DepMap) accelerates this field by systematically identifying cancer vulnerabilities in diverse preclinical models. Data from over 1,300 cell lines ha...
Cancer genomicsCancer models
10.1038/S41586-026-10843-7
ISSN:0028-0836
Paired tumor-normal sequencing provides insights into the CDKN2A-associated tumor spectrum
Kelsey E. Breen•Nikita Mehta•Vignesh Ravichandran•Miika Mehine•Chuan Gao等 26 人
Npj Precision Oncology
2025
•2025/11/19
•Vol.9 No.1 p.3630
Germline pathogenic variants (PV) in CDKN2A are characterized by an increased risk for melanoma, pancreatic cancer, nervous system tumors, and additional cancer types. We sought to define the tumor and clinical characteristics in a cohort of cancer patients with CDKN2A PV. Amongst 71,868 patients, 6...
Cancer geneticsCancer screeningGenetic testing
10.1038/S41698-025-01155-6
ISSN:2397-768X
Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance
Hao Zheng•Jinming Liu•Qi Cheng•Qianping Zhang•Yaoyao Zhang等 22 人
Nature Cancer
2024
•2024/1/30
•00 p.1-18
Acquired drug resistance is a major challenge for cancer therapy and is the leading cause of cancer mortality; however, the mechanisms of drug resistance are diverse and the strategy to specifically target drug-resistant cancer cells remains an unmet clinical issue. Here, we established a colorectal...
CancerGastrointestinal cancer
10.1038/S43018-023-00715-8
ISSN:2662-1347
TRMT112 drives a tumor growth and metastasis-promoting program in triple-negative breast cancer
Amr R. Elhamamsy•Brandon J. Metge•Mohamed H. Elbahoty•Bhavyasree Papineni•Heba Allah M. Alsheikh等 8 人
Cell Death & Differentiation
2026
•2026/1/8
•00 p.1-11
Ribosomal RNA Modifying Proteins (RRMPs) are integral to ribosome biogenesis, executing post-transcriptional modifications that influence translation fidelity and efficiency. Dysregulation of RRMPs has been increasingly implicated in cancer progression, yet their collective role across malignancies ...
MetastasisTumour biomarkers
10.1038/S41418-025-01643-Z
ISSN:1350-9047
Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis
Yan Fu•Keyu Shen•Hao Wang•Shun Wang•Xufeng Wang等 11 人
Signal Transduction And Targeted Therapy
2024
•2024/3/8
•Vol.9 No.1 p.1-16
Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a “neural addiction” property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through ne...
Gastrointestinal cancerMetastasis
10.1038/S41392-024-01761-Z
ISSN:2059-3635
Inhibition of CK1ε potentiates the therapeutic efficacy of CDK4/6 inhibitor in breast cancer
Dang Fabin•Nie Li•Zhou Jin•Shimizu Kouhei•Chu Chen等 16 人
Nature Communications
2021
•2021/9/10
•Vol.12 No.1 p.1-15
Although inhibitors targeting CDK4/6 kinases (CDK4/6i) have shown promising clinical prospect in treating ER+/HER2- breast cancers, acquired drug resistance is frequently observed and mechanistic knowledge is needed to harness their full clinical potential. Here, we report that inhibition of CDK4/6 ...
KinasesTumour-suppressor proteinsUbiquitin ligasesUbiquitylation
10.1038/S41467-021-25700-6
ISSN:2041-1723
TRMT6-mediated tRNA m1A modification acts as a translational checkpoint of histone synthesis and facilitates colorectal cancer progression
En-Wei Tao•Ye Wang•Juan Tan•Yan Chen•Tian-Yue Sun等 16 人
Nature Cancer
2025
•2025/6/3
•00 p.1-19
Transfer RNA modifications have emerged as critical regulators of translational reprogramming, yet their roles in colorectal cancer (CRC) remain largely elusive. Here, we find that tRNA N1-methyladenosine (m1A) methyltransferase TRMT6 is upregulated in human CRC tissues and high TRMT6 expression cor...
CancerColorectal cancerTranslationtRNAs
10.1038/S43018-025-00977-4
ISSN:2662-1347
TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
Gibson Shayin V.•Tomas Bort Elena•Rodríguez-Fernández Lucía•Allen Michael D.•Gomm Jennifer J.等 15 人
Npj Breast Cancer
2023
•2023/3/2
•Vol.9 No.1 p.1-15
Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. Virtually all women with DCIS are treated, despite evidence suggesting up to half would remain with stable, non-threatening, disease. Overtreatment thus presents a pressing issue in DCIS management. To understand ...
Breast cancerExtracellular matrix
10.1038/S41523-023-00513-6
ISSN:2374-4677
Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling
Sebastijan Hobor•Maise Al Bakir•Crispin T. Hiley•Marcin Skrzypski•Alexander M. Frankell等 47 人
Nature Communications
2024
•2024/6/13
•Vol.15 No.1 p.1-21
The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung...
Cancer geneticsNon-small-cell lung cancer
10.1038/S41467-024-47606-9
ISSN:2041-1723
9p21 loss confers a cold tumor immune microenvironment and primary resistance to immune checkpoint therapy
Han Guangchun•Yang Guoliang•Hao Dapeng•Lu Yang•Thein Kyaw等 32 人
Nature Communications
2021
•2021/9/23
•Vol.12 No.1 p.1-19
Immune checkpoint therapy (ICT) provides substantial clinical benefits to cancer patients, but a large proportion of cancers do not respond to ICT. To date, the genomic underpinnings of primary resistance to ICT remain elusive. Here, we performed immunogenomic analysis of data from TCGA and clinical...
Cancer immunotherapyCancer microenvironment
10.1038/S41467-021-25894-9
ISSN:2041-1723
Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer
Lopez Andrea•Reyna Denis E.•Gitego Nadege•Kopp Felix•Zhou Hua等 12 人
Nature Communications
2022
•2022/3/7
•Vol.13 No.1 p.1-18
Deregulation of the BCL-2 family interaction network ensures cancer resistance to apoptosis and is a major challenge to current treatments. Cancer cells commonly evade apoptosis through upregulation of the BCL-2 anti-apoptotic proteins; however, more resistant cancers also downregulate or inactivate...
ApoptosisTarget validationTargeted therapies
10.1038/S41467-022-28741-7
ISSN:2041-1723
Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer
Gillian Vandekerkhove•Jean-Michel Lavoie•Matti Annala•Andrew J. Murtha•Nora Sundahl等 20 人
Nature Communications
2021
•2021/1/8
•Vol.12 No.1 p.1-12
Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating ...
Bladder cancerCancer genomics
10.1038/S41467-020-20493-6
ISSN:2041-1723
Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling
David Kim•Chad M. Vanderbilt•Soo-Ryum Yang•Subhiksha Nandakumar•Khedoudja Nafa等 15 人
Nature Communications
2025
•2025/1/2
•Vol.16 No.1 p.1-11
Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term e...
Cancer genomicsCancer screeningSurgical oncologyTargeted therapiesTumour biomarkers
10.1038/S41467-024-55456-8
ISSN:2041-1723
Moving towards genome-wide data integration for patient stratification with Integrate Any Omics
Shihao Ma•Andy G. X. Zeng•Benjamin Haibe-Kains•Anna Goldenberg•John E. Dick等 6 人
Nature Machine Intelligence
2025
•2025/1/23
•Vol.7 No.1 p.29-42
High-throughput omics profiling advancements have greatly enhanced cancer patient stratification. However, incomplete data in multi-omics integration present a substantial challenge, as traditional methods like sample exclusion or imputation often compromise biological diversity and dependencies. Fu...
Cancer genomicsData integration
10.1038/S42256-024-00942-3
ISSN:2522-5839
TP53-dependent toxicity of CRISPR/Cas9 cuts is differential across genomic loci and can confound genetic screening
Álvarez Miguel M.•Biayna Josep•Supek Fran
Nature Communications
2022
•2022/8/4
•Vol.13 No.1 p.1-14
CRISPR/Cas9 gene editing can inactivate genes in a precise manner. This process involves DNA double-strand breaks (DSB), which may incur a loss of cell fitness. We hypothesize that DSB toxicity may be variable depending on the chromatin environment in the targeted locus. Here, by analyzing...
CRISPR-Cas9 genome editingDouble-strand DNA breaksEpigenomicsHigh-throughput screeningSequence annotation
10.1038/S41467-022-32285-1
ISSN:2041-1723
Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity
Shi Xiaohan•Li Yunguang•Yuan Qiuyue•Tang Shijie•Guo Shiwei等 20 人
Nature Communications
2022
•2022/4/21
•Vol.13 No.1 p.1-16
Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility ...
Cancer epigeneticsCancer genomicsHigh-throughput screening
10.1038/S41467-022-29857-6
ISSN:2041-1723
TET2 lesions enhance the aggressiveness of CEBPA-mutant acute myeloid leukemia by rebalancing GATA2 expression
Elizabeth Heyes•Anna S. Wilhelmson•Anne Wenzel•Gabriele Manhart•Thomas Eder等 18 人
Nature Communications
2023
•2023/10/4
•Vol.14 No.1 p.1-18
The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; CEBPADM) in acute myeloid leukemia (AML) with a combination of hypermorphic N-terminal mutations (CEBPANT), promoting expression of the leukemia-associated p30 isoform, and amorphic C-terminal mutation...
Acute myeloid leukaemiaDNA methylation
10.1038/S41467-023-41927-X
ISSN:2041-1723
Specific regulation of BACH1 by the hotspot mutant p53R175H reveals a distinct gain-of-function mechanism
Su Zhenyi•Kon Ning•Yi Jingjie•Zhao Haiqing•Zhang Wanwei等 17 人
Nature Cancer
2023
•2023/3/27
•00 p.1-18
Although the gain of function (GOF) of p53 mutants is well recognized, it remains unclear whether different p53 mutants share the same cofactors to induce GOFs. In a proteomic screen, we identified BACH1 as a cellular factor that recognizes the p53 DNA-binding domain depending on its mutation status...
CancerCell deathMetastasis
10.1038/S43018-023-00532-Z
ISSN:2662-1347
GAS41 modulates ferroptosis by anchoring NRF2 on chromatin
Zhe Wang•Xin Yang•Delin Chen•Yanqing Liu•Zhiming Li等 10 人
Nature Communications
2024
•2024/3/21
•Vol.15 No.1 p.1-16
YEATS domain-containing protein GAS41 is a histone reader and oncogene. Here, through genome-wide CRISPR-Cas9 screenings, we identify GAS41 as a repressor of ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recogni...
Cell deathEpigeneticsHigh-throughput screeningNon-small-cell lung cancerTranscription
10.1038/S41467-024-46857-W
ISSN:2041-1723
Small-molecule inhibition of kinesin KIF18A reveals a mitotic vulnerability enriched in chromosomally unstable cancers
Marc Payton•Brian Belmontes•Kelly Hanestad•Jodi Moriguchi•Kui Chen等 29 人
Nature Cancer
2023
•2023/12/27
•00 p.1-19
Chromosomal instability (CIN) is a hallmark of cancer, caused by persistent errors in chromosome segregation during mitosis. Aggressive cancers like high-grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC) have a high frequency of CIN and TP53 mutations. Here, we show that i...
CancerTarget identification
10.1038/S43018-023-00699-5
ISSN:2662-1347
High-resolution characterization of gene function using single-cell CRISPR tiling screen
Lu Yang•Anthony K. N. Chan•Kazuya Miyashita•Christopher D. Delaney•Xi Wang等 26 人
Nature Communications
2021
•2021/7/1
•Vol.12 No.1 p.1-9
Identification of novel functional domains and characterization of detailed regulatory mechanisms in cancer-driving genes is critical for advanced cancer therapy. To date, CRISPR gene editing has primarily been applied to defining the role of individual genes. Recently, high-density mutagenesis via ...
Cancer geneticsCRISPR-Cas systemsEpigeneticsHigh-throughput screening
10.1038/S41467-021-24324-0
ISSN:2041-1723
Determinants of renal cell carcinoma invasion and metastatic competence
Kim Kangsan•Zhou Qinbo•Christie Alana•Stevens Christina•Ma Yuanqing等 25 人
Nature Communications
2021
•2021/10/4
•Vol.12 No.1 p.1-12
Metastasis is the principal cause of cancer related deaths. Tumor invasion is essential for metastatic spread. However, determinants of invasion are poorly understood. We addressed this knowledge gap by leveraging a unique attribute of kidney cancer. Renal tumors invade into large vessels forming tu...
Cancer genomicsMetastasisRenal cell carcinoma
10.1038/S41467-021-25918-4
ISSN:2041-1723
Saturation genome editing maps the functional spectrum of pathogenic VHL alleles
Megan Buckley•Chloé Terwagne•Athina Ganner•Laura Cubitt•Reid Brewer等 18 人
Nature Genetics
2024
•2024/7/5
•Vol.56 No.7 p.1446-1455
To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel–Lindautumor suppressor (VHL). VHL encodes an E3 u...
Genetic testingMedical geneticsMutagenesisPersonalized medicineRenal cell carcinoma
10.1038/S41588-024-01800-Z
ISSN:1061-4036
Reversible epigenetic alterations regulate class I HLA loss in prostate cancer
Rodems Tamara S.•Heninger Erika•Stahlfeld Charlotte N.•Gilsdorf Cole S.•Carlson Kristin N.等 13 人
Communications Biology
2022
•2022/9/1
•Vol.5 No.1 p.1-16
Downregulation of HLA class I (HLA-I) impairs immune recognition and surveillance in prostate cancer and may underlie the ineffectiveness of checkpoint blockade. However, the molecular mechanisms regulating HLA-I loss in prostate cancer have not been fully explored. Here, we conducted a comprehensiv...
Cancer epigeneticsProstate cancerTumour immunology
10.1038/S42003-022-03843-6
ISSN:2399-3642
Patient-derived mini-colons enable long-term modeling of tumor–microenvironment complexity
L. Francisco Lorenzo-Martín•Nicolas Broguiere•Jakob Langer•Lucie Tillard•Mikhail Nikolaev等 8 人
Nature Biotechnology
2024
•2024/7/2
•00 p.1-10
Existing organoid models fall short of fully capturing the complexity of cancer because they lack sufficient multicellular diversity, tissue-level organization, biological durability and experimental flexibility. Thus, many multifactorial cancer processes, especially those involving the tumor microe...
Biomedical engineeringCancer modelsColorectal cancerPhenotypic screeningTissues
10.1038/S41587-024-02301-4
ISSN:1087-0156
NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression
Tejaswini Reddy•Akshjot Puri•Liliana Guzman-Rojas•Christoforos Thomas•Wei Qian等 27 人
Nature Communications
2024
•2024/12/30
•Vol.15 No.1 p.1-18
Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy...
Breast cancerCancer therapyCell signalling
10.1038/S41467-024-54651-X
ISSN:2041-1723
AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity
Emiliano Maiani•Giacomo Milletti•Francesca Nazio•Søs Grønbæk Holdgaard•Jirina Bartkova等 46 人
Nature
2021
•2021/4/14
•Vol.592 No.7856 p.799-803
Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in pa...
CheckpointsTumour-suppressor proteins
10.1038/S41586-021-03422-5
ISSN:0028-0836
Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers
Van Nyen Tom•Planque Mélanie•van Wagensveld Lilian•Duarte Joao A. G.•Zaal Esther A.等 25 人
Nature Communications
2022
•2022/8/5
•Vol.13 No.1 p.1-19
Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, including epithelial ovarian cancer. Patients often experience several response-relapse events, until tumors become resistant and life expectancy drops to 12–15 months. Despite improved knowledge of the ...
Cancer metabolismOvarian cancer
10.1038/S41467-022-32272-6
ISSN:2041-1723
Spatial gene expression analysis reveals drivers of extremely early lymph node metastasis in breast cancer
Satoi Nagasawa•Keiko Kajiya•Erina Ishikawa•Akinori Kanai•Ayako Suzuki等 18 人
Npj Breast Cancer
2026
•2026/1/23
•Vol.12 No.1 p.280
Lymph node metastasis correlates with breast cancer prognosis; however, the cellular mechanisms underlying the earliest metastatic events remain unclear. In spatial transcriptomic analysis of a patient with breast cancer at single-cell resolution, we identified 30 tumor cells representing the initia...
CancerComputational biology and bioinformaticsOncology
10.1038/S41523-026-00897-1
ISSN:2374-4677
Sex and smoking bias in the selection of somatic mutations in human bladder
Ferriol Calvet•Raquel Blanco Martinez-Illescas•Ferran Muiños•Maria Tretiakova•Elena S. Latorre-Esteves等 17 人
Nature
2025
•2025/10/8
•00 p.1-9
Men are at higher risk of several cancer types than women1. For bladder cancer the risk is four times higher for reasons that are not clear2. Smoking is also a principal risk factor for several tumour types, including bladder cancer3. As tumourigenesis is driven by somatic mutations, we wondered whe...
Cancer epidemiologyCancer genomicsGenome informaticsUrological cancer
10.1038/S41586-025-09521-X
ISSN:0028-0836
Metabolism-based targeting of MYC via MPC-SOD2 axis-mediated oxidation promotes cellular differentiation in group 3 medulloblastoma
Martell Emma•Kuzmychova Helgi•Kaul Esha•Senthil Harshal•Chowdhury Subir Roy等 14 人
Nature Communications
2023
•2023/5/2
•Vol.14 No.1 p.1-26
Group 3 medulloblastoma (G3 MB) carries the worst prognosis of all MB subgroups. MYC oncoprotein is elevated in G3 MB tumors; however, the mechanisms that support MYC abundance remain unclear. Using metabolic and mechanistic profiling, we pinpoint a role for mitochondrial metabolism in regulating MY...
Cancer metabolismCNS cancerPaediatric cancerPost-translational modifications
10.1038/S41467-023-38049-9
ISSN:2041-1723
A disease model resource reveals core principles of tissue-specific cancer evolution
Sebastian Mueller•Niklas de Andrade Krätzig•Markus Tschurtschenthaler•Miguel G. Silva•Chiara Thordsen等 66 人
Nature
2026
•2026/2/25
•00 p.1-12
Oncogenes such as KRAS display marked tissue specificity in their oncogenic potential, genetic interactions and phenotypic effects, but the underlying determinants remain largely unresolved1–5. Here, to address these questions, we developed the Mouse Cancer Cell line Atlas, a broad-utility resource ...
Cancer geneticsCancer modelsOncogenes
10.1038/S41586-026-10187-2
ISSN:0028-0836
Pancancer outcome prediction via a unified weakly supervised deep learning model
Wei Yuan•Yijiang Chen•Biyue Zhu•Sen Yang•Jiayu Zhang等 37 人
Signal Transduction And Targeted Therapy
2025
•2025/9/3
•Vol.10 No.1 p.1-11
Accurate prognosis prediction is essential for guiding cancer treatment and improving patient outcomes. While recent studies have demonstrated the potential of histopathological images in survival analysis, existing models are typically developed in a cancer-specific manner, lack extensive external ...
CancerMedical imagingOutcomes researchPredictive medicine
10.1038/S41392-025-02374-W
ISSN:2059-3635
Genome-wide detection of enhancer-hijacking events from chromatin interaction data in rearranged genomes
Xiaotao Wang•Jie Xu•Baozhen Zhang•Ye Hou•Fan Song等 7 人
Nature Methods
2021
•2021/6/3
•Vol.18 No.6 p.661-668
Recent efforts have shown that structural variations (SVs) can disrupt three-dimensional genome organization and induce enhancer hijacking, yet no computational tools exist to identify such events from chromatin interaction data. Here, we develop NeoLoopFinder, a computational framework to identify ...
CancerComputational biology and bioinformatics
10.1038/S41592-021-01164-W
ISSN:1548-7091
In vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells
Gaurav Luthria•Ran Li•Stephanie Wang•Mark Prytyskach•Rainer H. Kohler等 9 人
Nature Communications
2020
•2020/7/14
•Vol.11 No.1 p.1-17
Microtubules (MTs) mediate mitosis, directional signaling, and are therapeutic targets in cancer. Yet in vivo analysis of cancer cell MT behavior within the tumor microenvironment remains challenging. Here we developed an imaging pipeline using plus-end tip tracking and intravital microscopy to quan...
Cancer microenvironmentCellular imagingMicrotubules
10.1038/S41467-020-17147-Y
ISSN:2041-1723
OncoMark: a high-throughput neural multi-task learning framework for comprehensive cancer hallmark quantification
Shreyansh Priyadarshi•Camellia Mazumder•Bhavesh Neekhra•Sayan Biswas•Debojyoti Chowdhury等 7 人
Communications Biology
2025
•2025/10/7
•Vol.8 No.1 p.1-12
Quantifying the biological processes that drive cancer progression remains a key challenge in oncology. Although the hallmarks of cancer provide a foundational framework for understanding tumor behavior, existing diagnostic tools rarely measure these hallmarks directly. Here we present a neural mult...
Cancer genomicsSoftware
10.1038/S42003-025-08727-Z
ISSN:2399-3642
Monocyte depletion enhances neutrophil influx and proneural to mesenchymal transition in glioblastoma
Chen Zhihong•Soni Nishant•Pinero Gonzalo•Giotti Bruno•Eddins Devon J.等 19 人
Nature Communications
2023
•2023/4/3
•Vol.14 No.1 p.1-24
Myeloid cells comprise the majority of immune cells in tumors, contributing to tumor growth and therapeutic resistance. Incomplete understanding of myeloid cells response to tumor driver mutation and therapeutic intervention impedes effective therapeutic design. Here, by leveraging CRISPR/Cas9-based...
Cancer microenvironmentCNS cancerTumour immunology
10.1038/S41467-023-37361-8
ISSN:2041-1723
Overcoming resistance to immune checkpoint therapy in PTEN-null prostate cancer by intermittent anti-PI3Kα/β/δ treatment
Qi Zhi•Xu Zihan•Zhang Liuzhen•Zou Yongkang•Li Jinping等 9 人
Nature Communications
2022
•2022/1/10
•Vol.13 No.1 p.1-17
Combining immune checkpoint therapy (ICT) and targeted therapy holds great promises for broad and long-lasting anti-cancer therapies. However, combining ICT with anti-PI3K inhibitors have been challenging because the multifaceted effects of PI3K on both cancer cells and immune cells within the tumor...
Cancer immunotherapyTargeted therapies
10.1038/S41467-021-27833-0
ISSN:2041-1723
Mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanoma
Patterson Andrew•Auslander Noam
Nature Communications
2022
•2022/9/19
•Vol.13 No.1 p.1-10
Immune Checkpoint Inhibitor (ICI) therapy has revolutionized treatment for advanced melanoma; however, only a subset of patients benefit from this treatment. Despite considerable efforts, the Tumor Mutation Burden (TMB) is the only FDA-approved biomarker in melanoma. However, the mechanisms underlyi...
Machine learningMelanomaTumour biomarkers
10.1038/S41467-022-32838-4
ISSN:2041-1723
Upregulation of POLE and proficient DNA repair are features of CIC::DUX4 sarcomas
Nathan D. Seligson•Anjali Paragji•Feha Shahalam•Binyam Yilma•James L. Chen
Npj Precision Oncology
2025
•2025/6/20
•Vol.9 No.1 p.1-7
CIC::DUX4 translocation-positive sarcomas (CDS) are rare, highly proliferative tumors associated with chemotherapy resistance. Without a clear understanding of the molecular pathways driving CDS, no effective treatment regimens have been developed. Here, we identify protection against DNA damage thr...
Paediatric cancerSarcoma
10.1038/S41698-025-00985-8
ISSN:2397-768X
Systemic rewiring of dendritic cells by melanoma-secreted midkine impairs immune surveillance and response to immune checkpoint blockade
Xavier Catena•Marta Contreras-Alcalde•Naiara Juan-Larrea•Daniela Cerezo-Wallis•Tonantzin G. Calvo等 18 人
Nature Cancer
2025
•2025/3/28
•00 p.1-20
Cutaneous melanomas express a high number of potential neoepitopes, yet a substantial fraction of melanomas shift into immunologically cold phenotypes. Using cellular systems, mouse models and large datasets, we identify the tumor-secreted growth factor midkine (MDK) as a multilayered inhibitor of a...
CancerCancer immunotherapyMelanomaTumour immunology
10.1038/S43018-025-00929-Y
ISSN:2662-1347
The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis
Liu Teng•Yu Chen Feng•Su Tang Guo•Pei Lin Wang•Teng Fei Qi等 25 人
Nature Communications
2021
•2021/6/18
•Vol.12 No.1 p.1-17
Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is u...
CancerCell growthLong non-coding RNAsRNA
10.1038/S41467-021-24099-4
ISSN:2041-1723
MAML1 drives Notch and Hedgehog oncogenic pathways by inhibiting Itch activity in triple-negative breast cancer
Sabrina Zema•Francesca Di Fazio•Maria Pelullo•Sara Di Savino•Bruna Cerbelli等 24 人
Cell Death & Differentiation
2025
•2025/11/21
•00 p.1-17
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous breast cancer subtype with poor patient outcomes. TNBC heterogeneity arises from multiple dysregulated pathways, including Notch and Hedgehog, which contribute to tumor initiation, progression, and drug resistance. Identifying c...
OncogenesUbiquitylation
10.1038/S41418-025-01613-5
ISSN:1350-9047
PBRM1 mutation and preliminary response to immune checkpoint blockade treatment in non-small cell lung cancer
Huaqiang Zhou•Jiaqing Liu•Yaxiong Zhang•Yan Huang•Jiayi Shen等 8 人
Npj Precision Oncology
2020
•2020/3/16
•Vol.4 No.1 p.1-4
Polybromo-1 (PBRM1) gene is a promising biomarker for immunotherapy in clear cell renal cell carcinoma. But to our knowledge, the frequency and clinical relevance of PBRM1 mutation in lung cancer remain unknown. We conducted a retrospective study to evaluate the prevalence of PBRM1 mutation and its ...
Cancer genomicsNon-small-cell lung cancerPredictive markers
10.1038/S41698-020-0112-3
ISSN:2397-768X
GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome
Tiberti Silvia•Catozzi Carlotta•Croci Ottavio•Ballerini Mattia•Cagnina Danilo等 28 人
Nature Communications
2022
•2022/11/8
•Vol.13 No.1 p.1-20
CD8+ T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils ex...
Colorectal cancerTumour immunology
10.1038/S41467-022-34467-3
ISSN:2041-1723
Loss of EMI1 compromises chromosome stability and is associated with cellular transformation in colonic epithelial cell contexts
Rubi Campos Gudiño•Nicole M. Neudorf•Demi Andromidas•Zelda Lichtensztejn•Kirk J. McManus
British Journal Of Cancer
2024
•2024/10/2
•00 p.1-13
Colorectal cancer (CRC) is still a leading cause of cancer deaths worldwide. Thus, identifying the aberrant genes and proteins underlying disease pathogenesis is critical to improve early detection methods and develop novel therapeutic strategies. Chromosome instability (CIN), or ongoing changes in ...
Cancer geneticsColorectal cancerGenetics research
10.1038/S41416-024-02855-9
ISSN:0007-0920
CRISPR-StAR enables high-resolution genetic screening in complex in vivo models
Esther C. H. Uijttewaal•Joonsun Lee•Annika Charlotte Sell•Naomi Botay•Gintautas Vainorius等 17 人
Nature Biotechnology
2024
•2024/12/16
•00 p.1-13
Pooled genetic screening with CRISPR–Cas9 has enabled genome-wide, high-resolution mapping of genes to phenotypes, but assessing the effect of a given genetic perturbation requires evaluation of each single guide RNA (sgRNA) in hundreds of cells to counter stochastic genetic drift and obtain robust ...
Cancer genomicsComparative genomicsFunctional genomicsHigh-throughput screening
10.1038/S41587-024-02512-9
ISSN:1087-0156
An artificial intelligence-based model for prediction of clonal hematopoiesis variants in cell-free DNA samples
Gustavo Arango-Argoty•Marzieh Haghighi•Gerald J. Sun•Elizabeth Y. Choe•Aleksandra Markovets等 8 人
Npj Precision Oncology
2025
•2025/5/20
•Vol.9 No.1 p.1-8
Circulating tumor DNA is a critical biomarker in cancer diagnostics, but its accurate interpretation requires careful consideration of clonal hematopoiesis (CH), which can contribute to variants in cell-free DNA and potentially obscure true tumor-derived signals. Accurate detection of somatic varian...
BiomarkersCancerComputational biology and bioinformatics
10.1038/S41698-025-00921-W
ISSN:2397-768X
Regression-based Deep-Learning predicts molecular biomarkers from pathology slides
Omar S. M. El Nahhas•Chiara M. L. Loeffler•Zunamys I. Carrero•Marko van Treeck•Fiona R. Kolbinger等 17 人
Nature Communications
2024
•2024/2/10
•Vol.15 No.1 p.1-13
Deep Learning (DL) can predict biomarkers from cancer histopathology. Several clinically approved applications use this technology. Most approaches, however, predict categorical labels, whereas biomarkers are often continuous measurements. We hypothesize that regression-based DL outperforms cla...
Cancer imagingImage processingMachine learningPrognostic markersTumour biomarkers
10.1038/S41467-024-45589-1
ISSN:2041-1723
An integrated tumor, immune and microbiome atlas of colon cancer
Jessica Roelands•Peter J. K. Kuppen•Eiman I. Ahmed•Raghvendra Mall•Tariq Masoodi等 43 人
Nature Medicine
2023
•2023/5/19
•Vol.29 No.5 p.1273-1286
The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassi...
Colon cancerMicrobiomeT cellsTumour immunology
10.1038/S41591-023-02324-5
ISSN:1078-8956
EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma
Runping Fang•Xin Chen•Sicong Zhang•Hui Shi•Youqiong Ye等 12 人
Nature Communications
2021
•2021/1/8
•Vol.12 No.1 p.1-17
Glioblastoma (GBM) is the most common type of adult malignant brain tumor, but its molecular mechanisms are not well understood. In addition, the knowledge of the disease-associated expression and function of YTHDF2 remains very limited. Here, we show that YTHDF2 overexpression clinically correlates...
CNS cancerRNA metabolism
10.1038/S41467-020-20379-7
ISSN:2041-1723
ZNF92, an unexplored transcription factor with remarkably distinct breast cancer over-expression associated with prognosis and cell-of-origin
Kamran Mohammad•Bhattacharya Udayan•Omar Mohamed•Marchionni Luigi•Ince Tan A.
Npj Breast Cancer
2022
•2022/8/29
•Vol.8 No.1 p.1-11
Tumor phenotype is shaped both by transforming genomic alterations and the normal cell-of-origin. We identified a cell-of-origin associated prognostic gene expression signature, ET-9, that correlates with remarkably shorter overall and relapse free breast cancer survival, 8.7 and 6.2 years respectiv...
MetastasisPrognostic markers
10.1038/S41523-022-00474-2
ISSN:2374-4677
Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma
Coy Shannon•Wang Shu•Stopka Sylwia A.•Lin Jia-Ren•Yapp Clarence等 23 人
Nature Communications
2022
•2022/8/16
•Vol.13 No.1 p.1-24
How the glioma immune microenvironment fosters tumorigenesis remains incompletely defined. Here, we use single-cell RNA-sequencing and multiplexed tissue-imaging to characterize the composition, spatial organization, and clinical significance of extracellular purinergic signaling in glioma. We show ...
Cancer metabolismCancer microenvironmentCNS cancerTumour biomarkers
10.1038/S41467-022-32430-W
ISSN:2041-1723
Transcriptional control of CBX5 by the RNA-binding proteins RBMX and RBMXL1 maintains chromatin state in myeloid leukemia
Camila Prieto•Diu T. T. Nguyen•Zhaoqi Liu•Justin Wheat•Alexendar Perez等 22 人
Nature Cancer
2021
•2021/7/5
•00 p.1-17
RNA-binding proteins (RBPs) are key arbiters of post-transcriptional regulation and are found to be dysregulated in hematological malignancies. Here we identify the RBP RNA-binding motif protein, X-linked (RBMX; also known as hnRNPG), and its retrogene RBMXL1 to be required for murine and human myel...
Acute myeloid leukaemiaCancerCancer modelsChronic myeloid leukaemiaRNA
10.1038/S43018-021-00220-W
ISSN:2662-1347
Ageing promotes metastasis via activation of the integrated stress response
Angana A. H. Patel•Jozefina J. Dzanan•Kevin X. Ali•Ella A. Eklund•Samantha W. Alvarez等 29 人
Nature
2026
•2026/3/11
•00 p.1-10
Lung cancer predominantly affects older individuals, yet how physiological ageing influences tumour evolution remains poorly understood1. Here we show that ageing reprograms the evolutionary trajectory of KRAS-driven lung adenocarcinoma, limiting primary tumour growth while promoting metastatic diss...
AgeingCancer metabolismMechanisms of diseaseMetastasisNon-small-cell lung cancer
10.1038/S41586-026-10216-0
ISSN:0028-0836
Generating crossmodal gene expression from cancer histopathology improves multimodal AI predictions
Samiran Dey•Christopher R. S. Banerji•Partha Basuchowdhuri•Sanjoy K. Saha•Deepak Parashar等 6 人
Nature Communications
2025
•2025/12/31
0Emerging research has highlighted that artificial intelligence-based multimodal fusion of digital pathology and transcriptomic features can improve cancer diagnosis (grading/subtyping) and prognosis (survival risk) prediction. However, such direct fusion is impractical in clinical settings, where hi...
Cancer genomicsCancer imagingComputational scienceMachine learningPathology
10.1038/S41467-025-66961-9
ISSN:2041-1723
Validation of MSIntuit as an AI-based pre-screening tool for MSI detection from colorectal cancer histology slides
Charlie Saillard•Rémy Dubois•Oussama Tchita•Nicolas Loiseau•Thierry Garcia等 19 人
Nature Communications
2023
•2023/11/6
•Vol.14 No.1 p.1-11
Mismatch Repair Deficiency (dMMR)/Microsatellite Instability (MSI) is a key biomarker in colorectal cancer (CRC). Universal screening of CRC patients for MSI status is now recommended, but contributes to increased workload for pathologists and delayed therapeutic decisions. Deep learning has the pot...
Colorectal cancerPredictive markers
10.1038/S41467-023-42453-6
ISSN:2041-1723
Histopathology based AI model predicts anti-angiogenic therapy response in renal cancer clinical trial
Jay Jasti•Hua Zhong•Vandana Panwar•Vipul Jarmale•Jeffrey Miyata等 15 人
Nature Communications
2025
•2025/3/17
•Vol.16 No.1 p.1-13
Anti-angiogenic (AA) therapy is a cornerstone of metastatic clear cell renal cell carcinoma (ccRCC) treatment, but not everyone responds, and predictive biomarkers are lacking. CD31, a marker of vasculature, is insufficient, and the Angioscore, an RNA-based angiogenesis quantification method, is cos...
Machine learningRenal cell carcinomaTumour biomarkers
10.1038/S41467-025-57717-6
ISSN:2041-1723
A vision–language foundation model for precision oncology
Jinxi Xiang•Xiyue Wang•Xiaoming Zhang•Yinghua Xi•Feyisope Eweje等 18 人
Nature
2025
•2025/1/8
•00 p.1-10
Clinical decision-making is driven by multimodal data, including clinical notes and pathological characteristics. Artificial intelligence approaches that can effectively integrate multimodal data hold significant promise in advancing clinical care1,2. However, the scarcity of well-annotated multimod...
Machine learningOutcomes researchPathologyPrognosis
10.1038/S41586-024-08378-W
ISSN:0028-0836
Biology-aware mutation-based deep learning for outcome prediction of cancer immunotherapy with immune checkpoint inhibitors
Junyan Liu•Md Tauhidul Islam•Shengtian Sang•Liang Qiu•Lei Xing
Npj Precision Oncology
2023
•2023/11/6
•Vol.7 No.1 p.1-10
The response rate of cancer immune checkpoint inhibitors (ICI) varies among patients, making it challenging to pre-determine whether a particular patient will respond to immunotherapy. While gene mutation is critical to the treatment outcome, a framework capable of explicitly incorporating biology k...
CancerComputational biology and bioinformatics
10.1038/S41698-023-00468-8
ISSN:2397-768X
U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutations
David M. Walter•Katherine Cho•Smruthy Sivakumar•Daniel Denney•Iris T. Lee等 12 人
Nature Genetics
2026
•2026/7/1
•00 p.1-11
The mechanisms by which mutations of splicing factor gene U2AF1 contribute to lung adenocarcinoma pathogenesis are not well understood. Here we used prime editing to modify the endogenous U2AF1 gene in lung adenocarcinoma cells and assessed the impact on alternative splicing. One specific KRAS mutat...
Gene regulationNon-small-cell lung cancerOncogenesTranscriptomics
10.1038/S41588-026-02648-1
ISSN:1061-4036
AI-enabled virtual spatial proteomics from histopathology for interpretable biomarker discovery in lung cancer
Zhe Li•Yuchen Li•Jinxi Xiang•Xiyue Wang•Sen Yang等 20 人
Nature Medicine
2026
•2026/1/5
•Vol.32 No.1 p.231-244
Spatial proteomics enables high-resolution mapping of protein expression and can transform our understanding of biology and disease. However, major challenges remain for clinical translation, including cost, complexity and scalability. Here we present H&E to protein expression (HEX), an AI model...
Cancer immunotherapyNon-small-cell lung cancerPrognostic markers
10.1038/S41591-025-04060-4
ISSN:1078-8956
53BP1 loss elicits cGAS-STING-dependent antitumor immunity in ovarian and pancreatic cancer
Yajie Sun•Jeffrey Patterson-Fortin•Sen Han•Zhe Li•Zuzanna Nowicka等 12 人
Nature Communications
2024
•2024/8/6
•Vol.15 No.1 p.1-16
53BP1 nucleates the anti-end resection machinery at DNA double-strand breaks, thereby countering BRCA1 activity. Loss of 53BP1 leads to DNA end processing and homologous recombination in BRCA1-deficient cells. Consequently, BRCA1-mutant tumors, typically sensitive to PARP inhibitors (PARPi), become ...
Cancer immunotherapyDouble-strand DNA breaksOvarian cancerPancreatic cancer
10.1038/S41467-024-50999-2
ISSN:2041-1723
p120-catenin-dependent collective brain infiltration by glioma cell networks
Pavlo G. Gritsenko•Nader Atlasy•Cindy E. J. Dieteren•Anna C. Navis•Jan-Hendrik Venhuizen等 14 人
Nature Cell Biology
2020
•2020/1/6
•Vol.22 No.1 p.97-107
Diffuse brain infiltration by glioma cells causes detrimental disease progression, but its multicellular coordination is poorly understood. We show here that glioma cells infiltrate the brain collectively as multicellular networks. Contacts between moving glioma cells are adaptive epithelial-like or...
CancerCell-cycle proteinsCell migrationCNS cancer
10.1038/S41556-019-0443-X
ISSN:1465-7392
Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity
Megat H. B. A. Hamid•Pablo F. Cespedes•Chen Jin•Ji-Li Chen•Uzi Gileadi等 38 人
Nature Immunology
2024
•2024/4/1
•00 p.1-13
Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific imm...
Lymphocyte activationT cellsTumour immunology
10.1038/S41590-024-01802-3
ISSN:1529-2908
Genetic variations of DNA bindings of FOXA1 and co-factors in breast cancer susceptibility
Wen Wanqing•Chen Zhishan•Bao Jiandong•Long Quan•Shu Xiao-ou等 7 人
Nature Communications
2021
•2021/9/13
•Vol.12 No.1 p.1-12
Identifying transcription factors (TFs) whose DNA bindings are altered by genetic variants that regulate susceptibility genes is imperative to understand transcriptional dysregulation in disease etiology. Here, we develop a statistical framework to analyze extensive ChIP-seq and GWAS data and identi...
Breast cancerCancer epigenetics
10.1038/S41467-021-25670-9
ISSN:2041-1723
PPARα-mediated lipid metabolism reprogramming supports anti-EGFR therapy resistance in head and neck squamous cell carcinoma
Valentin Van den bossche•Julie Vignau•Engy Vigneron•Isabella Rizzi•Hannah Zaryouh等 30 人
Nature Communications
2025
•2025/2/1
•Vol.16 No.1 p.1-21
Anti-epidermal growth factor receptor (EGFR) therapy (cetuximab) shows a limited clinical benefit for patients with locally advanced or recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), due to the frequent occurrence of secondary resistance mechanisms. Here we report that cetuximab...
Cancer metabolismHead and neck cancer
10.1038/S41467-025-56675-3
ISSN:2041-1723
Metabolic targeting of cancer associated fibroblasts overcomes T-cell exclusion and chemoresistance in soft-tissue sarcomas
Marina T. Broz•Emily Y. Ko•Kristin Ishaya•Jinfen Xiao•Marco De Simone等 14 人
Nature Communications
2024
•2024/3/20
•Vol.15 No.1 p.1-18
T cell-based immunotherapies have exhibited promising outcomes in tumor control; however, their efficacy is limited in immune-excluded tumors. Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the tumor microenvironment and modulating immune infiltration. Despite the identification...
Cancer microenvironmentSarcomaTumour immunology
10.1038/S41467-024-46504-4
ISSN:2041-1723
Glycogen metabolism is dispensable for tumour progression in clear cell renal cell carcinoma
Hong Xie•Jun Song•Jason Godfrey•Romain Riscal•Nicolas Skuli等 7 人
Nature Metabolism
2021
•2021/3/23
•Vol.3 No.3 p.327-336
Glycogen accumulation is a highly consistent, distinguishable characteristic of clear cell renal cell carcinoma (ccRCC)1. While elevated glycogen pools might be advantageous for ccRCC cells in nutrient-deprived microenvironments to sustain tumour viability, data supporting a biological role for glyc...
Cancer metabolismMetabolismMetabolomicsUrological cancer
10.1038/S42255-021-00367-X
ISSN:2522-5812
Knowledge-guided adaptation of pathology foundation models effectively improves cross-domain generalization and demographic fairness
Yanyan Huang•Weiqin Zhao•Zhengyu Zhang•Yihang Chen•Yu Fu等 10 人
Nature Communications
2025
•2025/12/12
0Foundation models in computational pathology suffer from site-specific and demographic biases, which compromise their generalizability and fairness. We introduce FLEX, a framework that employs a task-specific information bottleneck, guided by visual and textual domain knowledge, to disentangle robus...
Cancer imagingComputer scienceMachine learningMedical imagingPathology
10.1038/S41467-025-66300-Y
ISSN:2041-1723
Metabolic gene alterations impact the clinical aggressiveness and drug responses of 32 human cancers
Musalula Sinkala•Nicola Mulder•Darren Patrick Martin
Communications Biology
2019
•2019/11/14
•Vol.2 No.1 p.1-14
Malignant cells reconfigure their metabolism to support oncogenic processes such as accelerated growth and proliferation. The mechanisms by which this occurs likely involve alterations to genes that encode metabolic enzymes. Here, using genomics data for 10,528 tumours of 32 different cancer types, ...
Biochemical reaction networksCancer genomicsData integrationTumour heterogeneity
10.1038/S42003-019-0666-1
ISSN:2399-3642
XPO1 inhibitor KPT-330 disrupts the core transcriptional regulatory circuitry of dedifferentiated liposarcoma by modulating the translation process
Xiaorui Fan•Ying Zhang•Zhengming Yang•Tuan Zea Tan•Xingze Huang等 14 人
Oncogene
2026
•2026/4/16
•00 p.1-17
Dedifferentiated liposarcoma (DDLPS) is a rare and aggressive subtype of liposarcoma, driven by a core transcriptional regulatory circuitry (CRC) that sustains tumor proliferation. This malignancy poses considerable clinical challenges, marked by high postoperative recurrence and metastatic potentia...
Cancer therapySarcoma
10.1038/S41388-026-03794-W
ISSN:0950-9232
Prostate lineage-specific metabolism governs luminal differentiation and response to antiandrogen treatment
Jenna M. Giafaglione•Preston D. Crowell•Amelie M. L. Delcourt•Takao Hashimoto•Sung Min Ha等 22 人
Nature Cell Biology
2023
•2023/12/4
•00 p.1-12
Lineage transitions are a central feature of prostate development, tumourigenesis and treatment resistance. While epigenetic changes are well known to drive prostate lineage transitions, it remains unclear how upstream metabolic signalling contributes to the regulation of prostate epithelial identit...
DifferentiationProstate cancer
10.1038/S41556-023-01274-X
ISSN:1465-7392
Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis
Jun Nishida•Yusaku Momoi•Kosuke Miyakuni•Yusuke Tamura•Kei Takahashi等 8 人
Nature Cell Biology
2020
•2020/3/23
•Vol.22 No.4 p.465-475
Advanced clear cell renal cell carcinoma (ccRCC) frequently causes systemic inflammation. Recent studies have shown that cancer cells reshape the immune landscape by secreting cytokines or chemokines. This phenotype, called cancer-cell-intrinsic inflammation, triggers a metastatic cascade. Here, we ...
Cancer epigeneticsInflammationMetastasisRenal cancer
10.1038/S41556-020-0491-2
ISSN:1465-7392
Histopathology images predict multi-omics aberrations and prognoses in colorectal cancer patients
Tsai Pei-Chen•Lee Tsung-Hua•Kuo Kun-Chi•Su Fang-Yi•Lee Tsung-Lu Michael等 21 人
Nature Communications
2023
•2023/4/13
•Vol.14 No.1 p.1-13
Histopathologic assessment is indispensable for diagnosing colorectal cancer (CRC). However, manual evaluation of the diseased tissues under the microscope cannot reliably inform patient prognosis or genomic variations crucial for treatment selections. To address these challenges, we develop the Mul...
Cancer imagingColorectal cancerDiagnostic markersMachine learningPrognostic markers
10.1038/S41467-023-37179-4
ISSN:2041-1723
Deep learning for dual detection of microsatellite instability and POLE mutations in colorectal cancer histopathology
Marco Gustav•Nic Gabriel Reitsam•Zunamys I. Carrero•Chiara M. L. Loeffler•Marko van Treeck等 18 人
Npj Precision Oncology
2024
•2024/5/23
•Vol.8 No.1 p.1-11
In the spectrum of colorectal tumors, microsatellite-stable (MSS) tumors with DNA polymerase ε (POLE) mutations exhibit a hypermutated profile, holding the potential to respond to immunotherapy similarly to their microsatellite-instable (MSI) counterparts. Yet, due to their rarity and the associated...
Diagnostic markersMathematics and computingPathologyTumour biomarkers
10.1038/S41698-024-00592-Z
ISSN:2397-768X
Transcript-targeted analysis reveals isoform alterations and double-hop fusions in breast cancer
Namba Shinichi•Ueno Toshihide•Kojima Shinya•Kobayashi Kenya•Kawase Katsushige等 17 人
Communications Biology
2021
•2021/11/22
•Vol.4 No.1 p.1-16
Although transcriptome alteration is an essential driver of carcinogenesis, the effects of chromosomal structural alterations on the cancer transcriptome are not yet fully understood. Short-read transcript sequencing has prevented researchers from directly exploring full-length transcripts, forcing ...
Breast cancerCancer genomicsRNA sequencing
10.1038/S42003-021-02833-4
ISSN:2399-3642
Converging deep learning and human-observed tumor-adipocyte interaction as a biomarker in colorectal cancer
Nic G. Reitsam•Bianca Grosser•David F. Steiner•Veselin Grozdanov•Ellery Wulczyn等 12 人
Communications Medicine
2024
•2024/8/15
•Vol.4 No.1 p.1-12
Tumor-Adipose-Feature (TAF) as well as SARIFA (Stroma AReactive Invasion Front Areas) are two histologic features/biomarkers linking tumor-associated adipocytes to poor outcomes in colorectal cancer (CRC) patients. Whereas TAF was identified by deep learning (DL) algorithms, SARIFA was established a...
Colorectal cancerComputational biology and bioinformatics
10.1038/S43856-024-00589-6
ISSN:2730-664X
Regulation of ribosomal gene expression and senescence by a PML-mTOR-RONIN nuclear complex in triple-negative breast cancer
Younes Medkour•Catherine Rosa Dufour•Lingwei Han•Phillipe Hutton•Mirna Farhat等 9 人
Oncogene
2025
•2025/11/8
•00 p.1-15
Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer that is associated with poor prognosis and a high risk of relapse, with limited treatment options. While the induction of senescence, a state of arrested cell growth, is generally achieved by available anticancer treat...
Breast cancerSenescenceTranscription
10.1038/S41388-025-03623-6
ISSN:0950-9232
YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells
Bai Yuchen•Gotz Carolin•Chincarini Ginevra•Zhao Zixuan•Slaney Clare等 13 人
Nature Communications
2023
•2023/3/22
•Vol.14 No.1 p.1-16
In heterogeneous head and neck cancer (HNC), subtype-specific treatment regimens are currently missing. An integrated analysis of patient HNC subtypes using single-cell sequencing and proteome profiles reveals an epithelial-mesenchymal transition (EMT) signature within the epithelial cancer-cell pop...
Epithelial–mesenchymal transitionHead and neck cancer
10.1038/S41467-023-37161-0
ISSN:2041-1723
Eph receptors and ephrins in cancer progression
Elena B. Pasquale
Nature Reviews Cancer
2023
•2023/11/23
•00 p.1-23
Evidence implicating Eph receptor tyrosine kinases and their ephrin ligands (that together make up the ‘Eph system’) in cancer development and progression has been accumulating since the discovery of the first Eph receptor approximately 35 years ago. Advances in the past decade and a half have ...
Cell signallingOncogenes
10.1038/S41568-023-00634-X
ISSN:1474-175X
Glioblastoma-instructed astrocytes suppress tumour-specific T cell immunity
Camilo Faust Akl•Brian M. Andersen•Zhaorong Li•Federico Giovannoni•Martin Diebold等 38 人
Nature
2025
•2025/5/21
•00 p.1-11
Glioblastoma is the most common and aggressive primary brain cancer and shows minimal response to therapies. The immunosuppressive tumour microenvironment in glioblastoma contributes to the limited therapeutic response. Astrocytes are abundant in the central nervous system and have important immunor...
NeuroimmunologyTumour immunology
10.1038/S41586-025-08997-X
ISSN:0028-0836
Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
Monteiro Cátia•Miarka Lauritz•Perea-García María•Priego Neibla•García-Gómez Pedro等 66 人
Nature Medicine
2022
•2022/4/11
•00 p.1-14
Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the li...
CNS cancerMetastasis
10.1038/S41591-022-01749-8
ISSN:1078-8956
Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus
Masashi Hashimoto•Shinji Kuroda•Nobuhiko Kanaya•Daisuke Kadowaki•Yusuke Yoshida等 20 人
British Journal Of Cancer
2024
•2024/2/5
•00 p.1-9
Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on...
Cancer immunotherapyImmunotherapy
10.1038/S41416-024-02583-0
ISSN:0007-0920
Intron retention is a robust marker of intertumoral heterogeneity in pancreatic ductal adenocarcinoma
Daniel J. Tan•Mithun Mitra•Alec M. Chiu•Hilary A. Coller
Npj Genomic Medicine
2020
•2020/12/11
•Vol.5 No.1 p.1-17
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate of <8%. Unsupervised clustering of 76 PDAC patients based on intron retention (IR) events resulted in two clusters of tumors (IR-1 and IR-2). While gene expression-based clusters are not predictive of patient...
Cancer genomicsGene regulatory networks
10.1038/S41525-020-00159-4
ISSN:2056-7944
Gene mutant dosage is associated with prognosis and metastatic tropism in 60,000 clinical cancer samples
Nicola Calonaci•Eriseld Krasniqi•Daniel Colic•Stefano Scalera•Giorgia Gandolfi等 13 人
Nature Genetics
2026
•2026/7/31
•00 p.1-12
The interplay between somatic mutations and copy number alterations influences tumor evolution and prognosis. These alterations are often treated independently, overlooking gene mutant dosage (GMD)—a key property of their interaction. Here we develop a computational framework that infers mutation co...
Data miningTumour biomarkers
10.1038/S41588-026-02666-Z
ISSN:1061-4036