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相关论文
143Single-cell transcriptomic and genomic changes in the ageing human brain
Ailsa M. Jeffries•Tianxiong Yu•Jennifer S. Ziegenfuss•Allie K. Tolles•Christina E. Baer等 9 人
Nature
2025
•2025/9/3
•00 p.1-10
Over time, cells in the brain and in the body accumulate damage, which contributes to the ageing process1. In the human brain, the prefrontal cortex undergoes age-related changes that can affect cognitive functioning later in life2. Here, using single-nucleus RNA sequencing (snRNA-seq), single-cell ...
Neural ageingSequencingTranscriptomics
10.1038/S41586-025-09435-8
ISSN:0028-0836
Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers
Kobayashi Yoshihisa•Chhoeu Chhayheng•Li Jiaqi•Price Kristin S.•Kiedrowski Lesli A.等 12 人
Nature
2022
•2022/3/2
•Vol.603 No.7900 p.335-342
RAS family members are the most frequently mutated oncogenes in human cancers. Although KRAS(G12C)-specific inhibitors show clinical activity in patients with cancer1–3, there are no direct inhibitors of NRAS, HRAS or non-G12C KRAS variants. Here we uncover the requirement of the silent KRASG60G mut...
Cancer geneticsRNA splicingTargeted therapies
10.1038/S41586-022-04451-4
ISSN:0028-0836
Cancer genomes tolerate deleterious coding mutations through somatic copy number amplifications of wild-type regions
Fabio Alfieri•Giulio Caravagna•Martin H. Schaefer
Nature Communications
2023
•2023/6/16
•Vol.14 No.1 p.1-13
Cancers evolve under the accumulation of thousands of somatic mutations and chromosomal aberrations. While most coding mutations are deleterious, almost all protein-coding genes lack detectable signals of negative selection. This raises the question of how tumors tolerate such large amounts of delet...
Cancer genomicsComputational biology and bioinformaticsEvolutionary theoryGene amplificationTumour heterogeneity
10.1038/S41467-023-39313-8
ISSN:2041-1723
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
Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting
Aurel Prosz•Pranshu Sahgal•Brandon M. Huffman•Zsofia Sztupinszki•Clare X. Morris等 23 人
Npj Precision Oncology
2024
•2024/4/8
•Vol.8 No.1 p.1-14
Homologous recombination (HR) and nucleotide excision repair (NER) are the two most frequently disabled DNA repair pathways in cancer. HR-deficient breast, ovarian, pancreatic and prostate cancers respond well to platinum chemotherapy and PARP inhibitors. However, the frequency of HR deficiency in g...
Cancer genomicsHigh-throughput screening
10.1038/S41698-024-00561-6
ISSN:2397-768X
Pan-cancer analysis reveals cooperativity of both strands of microRNA that regulate tumorigenesis and patient survival
Ramkrishna Mitra•Clare M. Adams•Wei Jiang•Evan Greenawalt•Christine M. Eischen
Nature Communications
2020
•2020/2/20
•Vol.11 No.1 p.1-15
Recently, both 5p and 3p miRNA strands are being recognized as functional instead of only one, leaving many miRNA strands uninvestigated. To determine whether both miRNA strands, which have different mRNA-targeting sequences, cooperate to regulate pathways/functions across cancer types, we evaluate ...
CancerComputational biology and bioinformaticsData integrationFunctional clusteringGene regulatory networks
10.1038/S41467-020-14713-2
ISSN:2041-1723
Prime editor-based high-throughput screening reveals functional synonymous mutations in human cells
Xuran Niu•Wei Tang•Yongshuo Liu•Binrui Mo•Ying Yu等 7 人
Nature Biotechnology
2025
•2025/6/24
•00 p.1-13
Synonymous mutations are generally considered neutral, while their roles in the human genome remain largely unexplored. Here we use the PEmax system to create a library of 297,900 engineered prime-editing guide RNAs and perform extensive screening to identify synonymous mutations affecting cell fitn...
High-throughput screeningMutagenesis
10.1038/S41587-025-02710-Z
ISSN:1087-0156
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
Targeting FSP1 to induce ferroptosis in chromophobe renal cell carcinoma
Samer Salem•Tiegang Han•Michel Alchoueiry•Nadine Mahmoud•Wafaa Bzeih等 13 人
Oncogene
2025
•2025/9/6
•00 p.1-12
There are no proven therapies for metastatic or unresectable Chromophobe Renal Cell Carcinoma (ChRCC). ChRCC is characterized by high glutathione levels and hypersensitivity to ferroptosis, an iron-dependent form of cell death characterized by peroxidation of polyunsaturated fatty acids. The underly...
Cancer therapyRenal cell carcinoma
10.1038/S41388-025-03562-2
ISSN:0950-9232
Pharmacological blockade of TEAD–YAP reveals its therapeutic limitation in cancer cells
Sun Yang•Hu Lu•Tao Zhipeng•Jarugumilli Gopala K.•Erb Hannah等 15 人
Nature Communications
2022
•2022/11/8
•Vol.13 No.1 p.1-18
Targeting TEAD autopalmitoylation has been proposed as a therapeutic approach for YAP-dependent cancers. Here we show that TEAD palmitoylation inhibitor MGH-CP1 and analogues block cancer cell “stemness”, organ overgrowth and tumor initiation in vitro and in vivo. MGH-CP1 sensitivity correlates sign...
Cancer therapeutic resistanceChemical biologyDrug discovery
10.1038/S41467-022-34559-0
ISSN:2041-1723
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
Genome-scale functional genomics identify genes preferentially essential for multiple myeloma cells compared to other neoplasias
Ricardo de Matos Simoes•Ryosuke Shirasaki•Sondra L. Downey-Kopyscinski•Geoffrey M. Matthews•Benjamin G. Barwick等 41 人
Nature Cancer
2023
•2023/5/26
•Vol.4 No.5 p.754-773
Clinical progress in multiple myeloma (MM), an incurable plasma cell (PC) neoplasia, has been driven by therapies that have limited applications beyond MM/PC neoplasias and do not target specific oncogenic mutations in MM. Instead, these agents target pathways critical for PC biology yet largely dis...
CancerCancer genomicsMyeloma
10.1038/S43018-023-00550-X
ISSN:2662-1347
Alanine supplementation exploits glutamine dependency induced by SMARCA4/2-loss
Xianbing Zhu•Zheng Fu•Shary Y. Chen•Dionzie Ong•Giulio Aceto等 28 人
Nature Communications
2023
•2023/5/20
•Vol.14 No.1 p.1-16
SMARCA4 (BRG1) and SMARCA2 (BRM) are the two paralogous ATPases of the SWI/SNF chromatin remodeling complexes frequently inactivated in cancers. Cells deficient in either ATPase have been shown to depend on the remaining counterpart for survival. Contrary to this paralog synthetic lethality, concomi...
Cancer metabolismMolecular biologyTargeted therapies
10.1038/S41467-023-38594-3
ISSN:2041-1723
Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions
Owen S. Skinner•Joan Blanco-Fernández•Russell P. Goodman•Akinori Kawakami•Hongying Shen等 12 人
Nature Metabolism
2023
•2023/5/17
•00 p.1-12
Glucose is vital for life, serving as both a source of energy and carbon building block for growth. When glucose is limiting, alternative nutrients must be harnessed. To identify mechanisms by which cells can tolerate complete loss of glucose, we performed nutrient-sensitized genome-wide genetic scr...
CarbohydratesMetabolismMetabolomics
10.1038/S42255-023-00774-2
ISSN:2522-5812
ELMO2 is a therapeutic vulnerability in mesenchymal-like and drug-resistant non-small cell lung cancer
Min Li•Ying Xue•Yuhan Chang•Fan Xu•Feizhen Wu等 14 人
Nature Communications
2026
•2026/4/17
0Epithelial-mesenchymal transition drives tumor metastasis and therapeutic resistance, yet few treatments have been developed that target this process. Here, we show that ELMO2 represents a specific vulnerability in mesenchymal-like cells. ELMO2 suppression induces excessive autophagy and cell death ...
Cancer therapy
10.1038/S41467-026-72062-Y
ISSN:2041-1723
Spi-1 proto-oncogene regulates mRNA hypertranscription and malignant progression in head and neck cancer
Zheran Liu•Zijian Qin•Huilin Li•Lili Zhu•Ling He等 10 人
Signal Transduction And Targeted Therapy
2026
•2026/3/18
•Vol.11 No.1 p.1020
Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent and lethal cancers worldwide. Despite multimodal therapeutic advances, long-term survival remains poor, underscoring the need to identify novel molecular drivers of disease aggressiveness. Hypertranscription is a genome-wide ...
Cancer genomicsHead and neck cancerTumour biomarkers
10.1038/S41392-026-02669-6
ISSN:2059-3635
Uncovering expression signatures of synergistic drug responses via ensembles of explainable machine-learning models
Janizek Joseph D.•Dincer Ayse B.•Celik Safiye•Chen Hugh•Chen William等 7 人
Nature Biomedical Engineering
2023
•2023/5/1
•00 p.1-19
Machine learning may aid the choice of optimal combinations of anticancer drugs by explaining the molecular basis of their synergy. By combining accurate models with interpretable insights, explainable machine learning promises to accelerate data-driven cancer pharmacology. However, owing to the hig...
Acute myeloid leukaemiaComputational models
10.1038/S41551-023-01034-0
ISSN:2157-846X
Distinct CDK6 complexes determine tumor cell response to CDK4/6 inhibitors and degraders
Xuewei Wu•Xiaobao Yang•Yan Xiong•Ruitong Li•Takahiro Ito等 19 人
Nature Cancer
2021
•2021/3/1
•00 p.1-15
Cyclin-dependent kinases (CDKs) 4 and 6 inhibitors (CDK4/6is) are effective in metastatic breast cancer, but they have been only modestly effective in most other tumor types. Here we show that tumors expressing low CDK6 rely on CDK4 function and are exquisitely sensitive to CDK4/6is. In contrast, tu...
CancerCancer therapeutic resistanceOncogenes
10.1038/S43018-021-00174-Z
ISSN:2662-1347
Acetyl-CoA biosynthesis drives resistance to histone acetyltransferase inhibition
Bishop Timothy R.•Subramanian Chitra•Bilotta Eric M.•Garnar-Wortzel Leopold•Ramos Anissa R.等 10 人
Nature Chemical Biology
2023
•2023/5/1
•00 p.1-8
Histone acetyltransferases (HATs) are implicated as both oncogene and nononcogene dependencies in diverse human cancers. Acetyl-CoA-competitive HAT inhibitors have emerged as potential cancer therapeutics and the first clinical trial for this class of drugs is ongoing (NCT04606446). Despite these de...
Cancer therapyChemical geneticsMechanism of actionMetabolic pathwaysSmall molecules
10.1038/S41589-023-01320-7
ISSN:1552-4450
KDM4C inhibition blocks tumor growth in basal breast cancer by promoting cathepsin L-mediated histone H3 cleavage
Zheqi Li•Guillermo Peluffo•Laura E. Stevens•Xintao Qiu•Marco Seehawer等 38 人
Nature Genetics
2025
•2025/6/2
•00 p.1-15
Basal breast cancer is a subtype with a poor prognosis in need of more effective therapeutic approaches. Here we describe a unique role for the KDM4C histone lysine demethylase in KDM4C-amplified basal breast cancers, where KDM4C inhibition reshapes chromatin and transcriptomic landscapes without su...
Breast cancerEpigenetics
10.1038/S41588-025-02197-Z
ISSN:1061-4036
Disentangling the architectural and non-architectural functions of CTCF and cohesin in gene regulation
Takeo Narita•Sinan Kilic•Yoshiki Higashijima•Natalie M. Scherer•Georgios Pappas等 7 人
Nature Genetics
2025
•2025/11/18
•00 p.1-15
Cohesin- and CTCF-mediated chromatin loops facilitate enhancer–promoter and promoter–promoter interactions, but their impact on global gene regulation remains debated. Here we show that acute removal of cohesin or CTCF in mouse cells dysregulates hundreds of genes. Cohesin depletion primarily downre...
EpigeneticsGene regulation
10.1038/S41588-025-02404-X
ISSN:1061-4036
Engineering NK and T cells with metabolite-sensing receptors to target solid tumors
Young-Min Kim•Min K. Tsai•Chang Sun•Olivia Laveroni•Reece Villarin Akana等 7 人
Nature Immunology
2026
•2026/3/23
•00 p.1-14
Natural killer (NK) cells and T cells need to infiltrate solid tumors to eradicate them. Here we show programmable mechanisms that can mobilize NK and T cells to solid tumors using metabolite-sensing receptors. In vivo and in vitro CRISPR activation screens using NK-92 cells identified GPR183, GPR84...
Applied immunologyChemotaxis
10.1038/S41590-026-02473-Y
ISSN:1529-2908
Systematic identification of biomarker-driven drug combinations to overcome resistance
Rees Matthew G.•Brenan Lisa•do Carmo Mariana•Duggan Patrick•Bajrami Besnik等 18 人
Nature Chemical Biology
2022
•2022/3/24
•00 p.1-10
The ability to understand and predict variable responses to therapeutic agents may improve outcomes in patients with cancer. We hypothesized that the basal gene-transcription state of cancer cell lines, coupled with cell viability profiles of small molecules, might be leveraged to nominate specific ...
Cancer therapyChemical geneticsData miningMechanism of actionSystems biology
10.1038/S41589-022-00996-7
ISSN:1552-4450
Flexynesis: A deep learning toolkit for bulk multi-omics data integration for precision oncology and beyond
Bora Uyar•Taras Savchyn•Amirhossein Naghsh Nilchi•Ahmet Sarigun•Ricardo Wurmus等 9 人
Nature Communications
2025
•2025/9/12
•Vol.16 No.1 p.1-18
Accurate decision making in precision oncology depends on integration of multimodal molecular information, for which various deep learning methods have been developed. However, most deep learning-based bulk multi-omics integration methods lack transparency, modularity, deployability, and are limited...
Cancer genomicsData integrationMachine learningSoftware
10.1038/S41467-025-63688-5
ISSN:2041-1723
DrBioRight 2.0: an LLM-powered bioinformatics chatbot for large-scale cancer functional proteomics analysis
Wei Liu•Jun Li•Yitao Tang•Yining Zhao•Chaozhong Liu等 12 人
Nature Communications
2025
•2025/3/6
•Vol.16 No.1 p.1-6
Functional proteomics provides critical insights into cancer mechanisms, facilitating the discovery of novel biomarkers and therapeutic targets. We have developed a comprehensive cancer functional proteomics resource using reverse phase protein arrays, incorporating data from nearly 8000 patient sam...
CancerComputational platforms and environmentsProteomics
10.1038/S41467-025-57430-4
ISSN:2041-1723
Tegavivint triggers TECR-dependent nonapoptotic cancer cell death
Logan Leak•Ziwei Wang•Alby J. Joseph•Brianna Johnson•Alyssa A. Chan等 26 人
Nature Chemical Biology
2025
•2025/5/26
•00 p.1-12
Small molecules that induce nonapoptotic cell death are of fundamental mechanistic interest and may be useful to treat certain cancers. Here we report that tegavivint, a drug candidate undergoing human clinical trials, can activate a unique mechanism of nonapoptotic cell death in sarcomas and other ...
Cell deathLipidomicsLipidsMechanism of actionSmall molecules
10.1038/S41589-025-01913-4
ISSN:1552-4450
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
PRMT inhibition induces a viral mimicry response in triple-negative breast cancer
Wu Qin•Nie David Y.•Ba-alawi Wail•Ji YiShuai•Zhang ZiWen等 29 人
Nature Chemical Biology
2022
•2022/5/16
•00 p.1-10
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), which has antitumor growth activity in TNBC. Pathway analysis of TNBC ...
Cancer therapyChemical geneticsRNA splicingScreening
10.1038/S41589-022-01024-4
ISSN:1552-4450
Histone methyltransferase KMT2D promotes castration-resistant prostate cancer progression by reactivating AR through FOXA1
Mayao Luo•Chenwei Wu•Manli Zhou•Rui Liu•Yifan Zhang等 11 人
Oncogene
2026
•2026/5/30
•00 p.1-17
Prostate cancer (PCa) progression, particularly to castration-resistant prostate cancer (CRPC), is driven by androgen receptor (AR) reactivation and epigenetic alterations. Here, we identify lysine methyltransferase 2D (KMT2D) as a critical epigenetic oncogene in PCa. KMT2D expression is elevated in...
Cancer metabolismEpigeneticsProstate cancer
10.1038/S41388-026-03828-3
ISSN:0950-9232
Genome-wide pooled CRISPR screening in neurospheres
Tanaz Abid•Amy B. Goodale•Zohra Kalani•Meghan Wyatt•Elizabeth M. Gonzalez等 13 人
Nature Protocols
2023
•2023/6/7
•00 p.1-18
Spheroid culture systems have allowed in vitro propagation of cells unable to grow in canonical cell culturing conditions, and may capture cellular contexts that model tumor growth better than current model systems. The insights gleaned from genome-wide clustered regularly interspaced short palindro...
Cancer geneticsFunctional genomicsHigh-throughput screening
10.1038/S41596-023-00835-6
ISSN:1754-2189
Pathway coessentiality mapping reveals complex II is required for de novo purine biosynthesis in acute myeloid leukaemia
Amy E. Stewart•Derek K. Zachman•Pol Castellano-Escuder•Lois M. Kelly•Ben Zolyomi等 19 人
Nature Metabolism
2025
•2025/12/5
•00 p.1-15
Understanding how cellular pathways interact is crucial for treating complex diseases like cancer. Individual gene–gene interaction studies have provided valuable insights, but may miss pathways working together. Here we develop a multi-gene approach to pathway mapping which reveals that acute myelo...
Acute myeloid leukaemiaCancer metabolismMetabolismMetabolomics
10.1038/S42255-025-01410-X
ISSN:2522-5812
METTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis
Su Rui•Dong Lei•Li Yangchan•Gao Min•He P. Cody等 32 人
Nature Cell Biology
2022
•2022/2/10
•Vol.24 No.2 p.205-216
METTL16 has recently been identified as an RNA methyltransferase responsible for the deposition of N6-methyladenosine (m6A) in a few transcripts. Whether METTL16 methylates a large set of transcripts, similar to METTL3 and METTL14, remains unclear. Here we show that METTL16 exerts both methyltransfe...
CancerRNA modificationTranslation
10.1038/S41556-021-00835-2
ISSN:1465-7392
DeepTarget predicts anti-cancer mechanisms of action of small molecules by integrating drug and genetic screens
Sanju Sinha•Neelam Sinha•Marlenne Perales•Adi Tarrab•Trinh Nguyen等 21 人
Npj Precision Oncology
2025
•2025/11/5
•Vol.9 No.1 p.1-14
Identifying the mechanisms of action (MOA) driving a drug’s anti-cancer efficacy is critical for its clinical success, guiding the search for its best biomarkers, indications and combinations. Yet, systematically identifying MOAs remains challenging due to drugs often engaging multiple targets with ...
Computational biology and bioinformaticsDrug discovery
10.1038/S41698-025-01111-4
ISSN:2397-768X
CRISPR screening by AAV episome-sequencing (CrAAVe-seq): a scalable cell-type-specific in vivo platform uncovers neuronal essential genes
Biswarathan Ramani•Indigo V. L. Rose•Noam Teyssier•Andrew Pan•Spencer Danner-Bocks等 11 人
Nature Neuroscience
2025
•2025/8/22
•00 p.1-12
There is a substantial need for scalable CRISPR-based genetic screening methods that can be applied in mammalian tissues in vivo while enabling cell-type-specific analysis. Here we developed an adeno-associated virus (AAV)-based CRISPR screening platform, CrAAVe-seq, that incorporates a Cre-sensitiv...
Functional genomicsGenetics of the nervous systemHigh-throughput screeningMolecular neuroscience
10.1038/S41593-025-02043-9
ISSN:1097-6256
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
A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing
Sinha Sanju•Barbosa Karina•Cheng Kuoyuan•Leiserson Mark D. M.•Jain Prashant等 13 人
Nature Communications
2021
•2021/11/11
•Vol.12 No.1 p.1-13
Recent studies have reported that genome editing by CRISPR–Cas9 induces a DNA damage response mediated by p53 in primary cells hampering their growth. This could lead to a selection of cells with pre-existing p53 mutations. In this study, employing an integrated computational and experimental framew...
CancerCRISPR-Cas9 genome editingComputational biology and bioinformatics
10.1038/S41467-021-26788-6
ISSN:2041-1723
Integrated chemical and genetic screens unveil FSP1 mechanisms of ferroptosis regulation
Toshitaka Nakamura•Eikan Mishima•Naoya Yamada•André Santos Dias Mourão•Dietrich Trümbach等 14 人
Nature Structural & Molecular Biology
2023
•2023/11/13
•Vol.30 No.11 p.1806-1815
Ferroptosis, marked by iron-dependent lipid peroxidation, may present an Achilles heel for the treatment of cancers. Ferroptosis suppressor protein-1 (FSP1), as the second ferroptosis mainstay, efficiently prevents lipid peroxidation via NAD(P)H-dependent reduction of quinones. Because its molecular...
Cell deathDrug discoveryEnzyme mechanisms
10.1038/S41594-023-01136-Y
ISSN:1545-9993
RCANE: a deep learning algorithm for whole-genome pan-cancer somatic copy number aberration prediction using RNA-seq data
Changhao Ge•Xiaowen Hu•Lin Zhang•Hongzhe Li
Communications Biology
2025
•2025/9/24
•Vol.8 No.1 p.1-10
Transcriptome sequencing (RNA-seq) of cancers is widely employed in cancer research to investigate gene expression patterns and their role in disease progression. Somatic copy-number aberrations (SCNAs)—critical genomic drivers of tumorigenesis—can also be inferred directly from RNA-seq, yielding a ...
Cancer genomicsComputational models
10.1038/S42003-025-08712-6
ISSN:2399-3642
The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis in urothelial bladder cancer
Dong Yan•Qingqing He•Lu Pei•Meihua Yang•Lifang Huang等 12 人
Cell Death & Disease
2023
•2023/8/12
•Vol.14 No.8 p.1-15
Urothelial bladder cancer (UBC) is one of the most prevalent malignancies worldwide, with striking tumor heterogeneity. Elucidating the molecular mechanisms that can be exploited for the treatment of aggressive UBC is a particularly relevant goal. Protein ubiquitination is a critical post-translatio...
Bladder cancerCell invasion
10.1038/S41419-023-06000-X
ISSN:2041-4889
Single cell multi-omics reveal intra-cell-line heterogeneity across human cancer cell lines
Qionghua Zhu•Xin Zhao•Yuanhang Zhang•Yanping Li•Shang Liu等 36 人
Nature Communications
2023
•2023/12/9
•Vol.14 No.1 p.1-21
Human cancer cell lines have long served as tools for cancer research and drug discovery, but the presence and the source of intra-cell-line heterogeneity remain elusive. Here, we perform single-cell RNA-sequencing and ATAC-sequencing on 42 and 39 human cell lines, respectively, to illustrate both t...
Cancer genomicsEpigenomicsTranscriptomics
10.1038/S41467-023-43991-9
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
The ETS transcription factor ETV6 constrains the transcriptional activity of EWS–FLI to promote Ewing sarcoma
Lu Diana Y.•Ellegast Jana M.•Ross Kenneth N.•Malone Clare F.•Lin Shan等 19 人
Nature Cell Biology
2023
•2023/1/19
•Vol.25 No.2 p.285-297
Transcription factors (TFs) are frequently mutated in cancer. Paediatric cancers exhibit few mutations genome-wide but frequently harbour sentinel mutations that affect TFs, which provides a context to precisely study the transcriptional circuits that support mutant TF-driven oncogenesis. A broadly ...
Cancer epigeneticsOncogenesSarcoma
10.1038/S41556-022-01059-8
ISSN:1465-7392
Pan-cancer single-cell RNA-seq identifies recurring programs of cellular heterogeneity
Gabriela S. Kinker•Alissa C. Greenwald•Rotem Tal•Zhanna Orlova•Michael S. Cuoco等 23 人
Nature Genetics
2020
•2020/10/30
•Vol.52 No.11 p.1208-1218
Cultured cell lines are the workhorse of cancer research, but the extent to which they recapitulate the heterogeneity observed among malignant cells in tumors is unclear. Here we used multiplexed single-cell RNA-seq to profile 198 cancer cell lines from 22 cancer types. We identified 12 expression p...
CancerSystems biologyTranscriptomics
10.1038/S41588-020-00726-6
ISSN:1061-4036
Synthetic essentiality between PTEN and core dependency factor PAX7 dictates rhabdomyosarcoma identity
Langdon Casey G.•Gadek Katherine E.•Garcia Matthew R.•Evans Myron K.•Reed Kristin B.等 15 人
Nature Communications
2021
•2021/9/17
•Vol.12 No.1 p.1-18
PTEN promoter hypermethylation is nearly universal and PTEN copy number loss occurs in ~25% of fusion-negative rhabdomyosarcoma (FN-RMS). Here we show Pten deletion in a mouse model of FN-RMS results in less differentiated tumors more closely resembling human embryonal RMS. PTEN loss activated the P...
Cancer modelsEmbryonal neoplasmsPaediatric cancerSarcomaTumour-suppressor proteins
10.1038/S41467-021-25829-4
ISSN:2041-1723
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
A self-adaptive and versatile tool for eliminating multiple undesirable variations from large-scale transcriptomes
Mengji Zhang•Lei Yan•Xinbo Wang•Yi Yuan•Shimin Zou等 17 人
Nature Biomedical Engineering
2025
•2025/7/25
•00 p.1-14
Accurate identification of true biological signals from diverse undesirable variations in large-scale transcriptomes is essential for downstream discoveries. Here we develop a universal deep neural network, called DeepAdapter, to eliminate various undesirable variations including batch, platform, pu...
Data integrationData miningGene expression
10.1038/S41551-025-01466-W
ISSN:2157-846X
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
Converging mechanism of UM171 and KBTBD4 neomorphic cancer mutations
Xiaowen Xie•Olivia Zhang•Megan J. R. Yeo•Ceejay Lee•Ran Tao等 23 人
Nature
2025
•2025/2/12
•Vol.639 No.8053 p.241-249
Cancer mutations can create neomorphic protein–protein interactions to drive aberrant function1,2. As a substrate receptor of the CULLIN3-RING E3 ubiquitin ligase complex, KBTBD4 is recurrently mutated in medulloblastoma3, the most common embryonal brain tumour in children4. These mutations impart g...
Cryoelectron microscopyMutagenesisPaediatric cancerSmall molecules
10.1038/S41586-024-08533-3
ISSN:0028-0836
Mitochondrial matrix RTN4IP1/OPA10 is an oxidoreductase for coenzyme Q synthesis
Isaac Park•Kwang-eun Kim•Jeesoo Kim•Ae-Kyeong Kim•Subin Bae等 18 人
Nature Chemical Biology
2023
•2023/10/26
•00 p.1-13
Targeting proximity-labeling enzymes to specific cellular locations is a viable strategy for profiling subcellular proteomes. Here, we generated transgenic mice (MAX-Tg) expressing a mitochondrial matrix-targeted ascorbate peroxidase. Comparative analysis of matrix proteomes from the muscle tissues ...
Chemical toolsEnzyme mechanismsMass spectrometryMetabolismProteomics
10.1038/S41589-023-01452-W
ISSN:1552-4450
An ALYREF-MYCN coactivator complex drives neuroblastoma tumorigenesis through effects on USP3 and MYCN stability
Zsuzsanna Nagy•Janith A. Seneviratne•Maxwell Kanikevich•William Chang•Chelsea Mayoh等 16 人
Nature Communications
2021
•2021/3/25
•Vol.12 No.1 p.1-20
To achieve the very high oncoprotein levels required to drive the malignant state cancer cells utilise the ubiquitin proteasome system to upregulate transcription factor levels. Here our analyses identify ALYREF, expressed from the most common genetic copy number variation in neuroblastoma, chromoso...
Cancer genomicsOncogenesPaediatric cancer
10.1038/S41467-021-22143-X
ISSN:2041-1723
Super enhancers define regulatory subtypes and cell identity in neuroblastoma
Moritz Gartlgruber•Ashwini Kumar Sharma•Andrés Quintero•Daniel Dreidax•Selina Jansky等 23 人
Nature Cancer
2020
•2020/12/7
•Vol.2 No.1 p.114-128
Half of the children diagnosed with neuroblastoma (NB) have high-risk disease, disproportionately contributing to overall childhood cancer-related deaths. In addition to recurrent gene mutations, there is increasing evidence supporting the role of epigenetic deregulation in disease pathogenesis. Yet...
Cancer genomicsPaediatric cancer
10.1038/S43018-020-00145-W
ISSN:2662-1347
A non-canonical tricarboxylic acid cycle underlies cellular identity
Arnold Paige K.•Jackson Benjamin T.•Paras Katrina I.•Brunner Julia S.•Hart Madeleine L.等 11 人
Nature
2022
•2022/3/9
•Vol.603 No.7901 p.477-481
The tricarboxylic acid (TCA) cycle is a central hub of cellular metabolism, oxidizing nutrients to generate reducing equivalents for energy production and critical metabolites for biosynthetic reactions. Despite the importance of the products of the TCA cycle for cell viability and proliferation, ma...
Cancer metabolismCell biologyCell growthEmbryonic stem cellsMetabolomics
10.1038/S41586-022-04475-W
ISSN:0028-0836
ATM counteracts chromatin-bound cGAS during DNA replication
Yunhao Song•Xiaojuan Ran•Yu Xu•Kartik Subramanian•Chao Dai等 9 人
Nature Cell Biology
2026
•2026/4/29
•00 p.1-11
Cyclic GMP–AMP synthase (cGAS), a DNA sensor that activates type-I interferon responses, is restrained in the nucleus through chromatin binding, but its impact on DNA metabolism remains unknown. Here we show that chromatin-bound cGAS impedes DNA replication forks unless countered by ATM. Upon ATM lo...
Cancer epigeneticsStalled forks
10.1038/S41556-026-01931-X
ISSN:1465-7392
Genetic suppression features ABHD18 as a Barth syndrome therapeutic target
Sanna N. Masud•Anchal Srivastava•Patricia Mero•Victoria Saba Echezarreta•Eve Anderson等 49 人
Nature
2025
•2025/9/3
•00 p.1-10
Cardiolipin (CL) is the signature phospholipid of the inner mitochondrial membrane, where it stabilizes electron transport chain protein complexes1. The final step in CL biosynthesis relates to its remodelling: the exchange of nascent acyl chains with longer, unsaturated chains1. However, the enzyme...
Genetic interactionHydrolasesMetabolic disorders
10.1038/S41586-025-09373-5
ISSN:0028-0836
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
Catalytic-independent functions of the Integrator–PP2A complex (INTAC) confer sensitivity to BET inhibition
Pengyu Fan•Xue-Ying Shang•Aixia Song•Shuo Chen•Run-Yuan Mao等 24 人
Nature Chemical Biology
2025
•2025/1/14
•00 p.1-12
Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins,...
Histone post-translational modificationsTranscription
10.1038/S41589-024-01807-X
ISSN:1552-4450
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
Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites
Paul Atanu•Annunziato Stefano•Lu Bo•Sun Tianliang•Evrova Olivera等 20 人
Nature Communications
2022
•2022/2/17
•Vol.13 No.1 p.1-14
The Hippo/YAP pathway controls cell proliferation through sensing physical and spatial organization of cells. How cell-cell contact is sensed by Hippo signaling is poorly understood. Here, we identified the cell adhesion molecule KIRREL1 as an upstream positive regulator of the mammalian Hippo pathw...
CRISPR-Cas9 genome editingCell adhesionCell signallingHIPPO signalling
10.1038/S41467-022-28567-3
ISSN:2041-1723
Integrating multimodal cancer data using deep latent variable path modelling
Alex Ing•Alvaro Andrades•Marco Raffaele Cosenza•Jan O. Korbel
Nature Machine Intelligence
2025
•2025/7/22
•Vol.7 No.7 p.1053-1075
Cancers are commonly characterized by a complex pathology encompassing genetic, microscopic and macroscopic features, which can be probed individually using imaging and omics technologies. Integrating these data to obtain a full understanding of pathology remains challenging. We introduce a method c...
Breast cancerComputer scienceData integrationMachine learning
10.1038/S42256-025-01052-4
ISSN:2522-5839
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
A first-generation pediatric cancer dependency map
Neekesh V. Dharia•Guillaume Kugener•Lillian M. Guenther•Clare F. Malone•Adam D. Durbin等 26 人
Nature Genetics
2021
•2021/3/22
•00 p.1-10
Exciting therapeutic targets are emerging from CRISPR-based screens of high mutational-burden adult cancers. A key question, however, is whether functional genomic approaches will yield new targets in pediatric cancers, known for remarkably few mutations, which often encode proteins considered chall...
CancerFunctional genomicsHigh-throughput screening
10.1038/S41588-021-00819-W
ISSN:1061-4036
Integrating transcription factor occupancy with transcriptome-wide association analysis identifies susceptibility genes in human cancers
He Jingni•Wen Wanqing•Beeghly Alicia•Chen Zhishan•Cao Chen等 9 人
Nature Communications
2022
•2022/11/19
•Vol.13 No.1 p.1-15
Transcriptome-wide association studies (TWAS) have successfully discovered many putative disease susceptibility genes. However, TWAS may suffer from inaccuracy of gene expression predictions due to inclusion of non-regulatory variants. By integrating prior knowledge of susceptible transcription fact...
Cancer geneticsGenetic association studyStatistical methods
10.1038/S41467-022-34888-0
ISSN:2041-1723
Targeting β-catenin degradation with GSK3β inhibitors induces cell death in acute lymphoblastic leukemia
Kadriye Nehir Cosgun•Huda Jumaa•Mark E. Robinson•Zhangliang Cheng•Salim Oulghazi等 23 人
Nature Cancer
2026
•2026/1/8
•Vol.7 No.1 p.150-168
As part of canonical Wnt signaling, T cell factor (TCF)–β-catenin complexes promote MYC-dependent proliferation. Lesions of the β-catenin protein degradation machinery are common oncogenic drivers. Here, we show that B cell acute lymphoblastic leukemia (B-ALL) lacks these mutations and critically de...
Acute lymphocytic leukaemiaCancerLymphomaProteasomeTranscriptional regulatory elements
10.1038/S43018-025-01093-Z
ISSN:2662-1347
Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma
Miyuki Nomura•Mai Ohuchi•Yoshimi Sakamoto•Kei Kudo•Keisuke Yaku等 29 人
Nature Communications
2023
•2023/12/13
•Vol.14 No.1 p.1-15
Nicotinamide phosphoribosyltransferase (NAMPT) plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and pros...
Cancer metabolismMetabolomics
10.1038/S41467-023-43630-3
ISSN:2041-1723
Systematic prioritization of functional variants and effector genes underlying colorectal cancer risk
Philip J. Law•James Studd•James Smith•Jayaram Vijayakrishnan•Bradley T. Harris等 9 人
Nature Genetics
2024
•2024/9/16
•00 p.1-8
Genome-wide association studies of colorectal cancer (CRC) have identified 170 autosomal risk loci. However, for most of these, the functional variants and their target genes are unknown. Here, we perform statistical fine-mapping incorporating tissue-specific epigenetic annotations and massively par...
Colorectal cancerFunctional genomics
10.1038/S41588-024-01900-W
ISSN:1061-4036
Loss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer
Irineos Papakyriacou•Ginte Kutkaite•Marta Rúbies Bedós•Divya Nagarajan•Liam P. Alford等 7 人
Nature Communications
2024
•2024/4/27
•Vol.15 No.1 p.1-19
Immune checkpoint blockade therapy aims to activate the immune system to eliminate cancer cells. However, clinical benefits are only recorded in a subset of patients. Here, we leverage genome-wide CRISPR/Cas9 screens in a Tumor-Immune co-Culture System focusing on triple-negative breast cancer (TNBC...
Breast cancerNeddylationTumour immunology
10.1038/S41467-024-47987-X
ISSN:2041-1723
Critical requirement of SOS1 for tumor development and microenvironment modulation in KRASG12D-driven lung adenocarcinoma
Fernando C. Baltanás•Rósula García-Navas•Pablo Rodríguez-Ramos•Nuria Calzada•Cristina Cuesta等 11 人
Nature Communications
2023
•2023/9/20
•Vol.14 No.1 p.1-16
The impact of genetic ablation of SOS1 or SOS2 is evaluated in a murine model of KRASG12D-driven lung adenocarcinoma (LUAD). SOS2 ablation shows some protection during early stages but only SOS1 ablation causes significant, specific long term increase of survival/lifespan of the KRASG12D mice associ...
Cancer microenvironmentNon-small-cell lung cancerOncogenes
10.1038/S41467-023-41583-1
ISSN:2041-1723
Non-coding genetic variants underlying higher prostate cancer risk in men of African ancestry
Shan Li•Kaniz Fatema•Nidharshan Sundarraj•Arashdeep Singh•Padma Sheila Rajagopal等 8 人
Nature Communications
2025
•2025/11/20
•Vol.16 No.1 p.102020
Prostate cancer (PrCa) incidence and severity vary across ancestries; men of African ancestry (AA) are more likely to be diagnosed and die from PrCa than those of European ancestry (EA). Current polygenic risk scores, even from multi-ancestry GWAS, do not fully capture population-specific genetic me...
Cancer geneticsGene regulationMachine learningProstate cancer
10.1038/S41467-025-64631-4
ISSN:2041-1723
HDAC3 genetic and pharmacologic inhibition radiosensitizes fusion positive rhabdomyosarcoma by promoting DNA double-strand breaks
Matteo Cassandri•Antonella Porrazzo•Silvia Pomella•Beatrice Noce•Clemens Zwergel等 30 人
Cell Death Discovery
2024
•2024/8/6
•Vol.10 No.1 p.1-20
Radiotherapy (RT) plays a critical role in the management of rhabdomyosarcoma (RMS), the prevalent soft tissue sarcoma in childhood. The high risk PAX3-FOXO1 fusion-positive subtype (FP-RMS) is often resistant to RT. We have recently demonstrated that inhibition of class-I histone deacetylases (HDAC...
Double-strand DNA breaksPaediatric cancerSarcoma
10.1038/S41420-024-02115-Y
ISSN:2058-7716
YAP/TAZ interacts with RBM39 to confer resistance against indisulam
Toshinori Ando•Kento Okamoto•Yume Ueda•Nanako Kataoka•Tomoaki Shintani等 8 人
Oncogenesis
2024
•2024/7/15
•Vol.13 No.1 p.1-8
The Hippo pathway and its downstream effectors, Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ), are essential for cell growth and organ development. Emerging evidence revealed that the Hippo pathway and YAP/TAZ are frequently dysregulated by multiple genetic alte...
Head and neck cancerHIPPO signalling
10.1038/S41389-024-00527-0
ISSN:2157-9024
Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study
Dongliang Bian•Liangdong Sun•Junjie Hu•Liang Duan•Haoran Xia等 21 人
Nature Communications
2023
•2023/8/3
•Vol.14 No.1 p.1-14
Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm...
Non-small-cell lung cancerPhase II trials
10.1038/S41467-023-40349-Z
ISSN:2041-1723
CRISPR screens identify PRMT7 as a therapeutic target to enhance T cell-mediated killing in breast cancer
Wei Shi•Yi Luo•Yizhuo Wang•Jacqueline M. Burrows•Debra Black等 17 人
Npj Breast Cancer
2026
•2026/1/21
•Vol.12 No.1 p.240
Genome-wide association studies (GWAS) have identified more than 220 loci associated with breast cancer susceptibility, yet identifying effector genes, their modes of action and prioritising therapeutic targets remains a significant challenge. To address this, we performed pooled CRISPR knockout and...
Breast cancerFunctional genomicsGenome-wide association studiesImmunosurveillance
10.1038/S41523-025-00888-8
ISSN:2374-4677
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
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
Diffusion kernel-based predictive modeling of KRAS dependency in KRAS wild type cancer cell lines
Ulmer Bastian•Odenthal Margarete•Buettner Reinhard•Roth Wilfried•Kloth Michael
Npj Systems Biology And Applications
2022
•2022/1/19
•Vol.8 No.1 p.1-11
Recent progress in clinical development of KRAS inhibitors has raised interest in predicting the tumor dependency on frequently mutated RAS-pathway oncogenes. However, even without such activating mutations, RAS proteins represent core components in signal integration of several membrane-bound kinas...
CancerComputational biology and bioinformaticsMolecular biology
10.1038/S41540-021-00211-8
ISSN:2056-7189
Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition
Yael Cohen-Sharir•James M. McFarland•Mai Abdusamad•Carolyn Marquis•Sara V. Bernhard等 26 人
Nature
2021
•2021/1/27
•Vol.590 No.7846 p.486-491
Selective targeting of aneuploid cells is an attractive strategy for cancer treatment1. However, it is unclear whether aneuploidy generates any clinically relevant vulnerabilities in cancer cells. Here we mapped the aneuploidy landscapes of about 1,000 human cancer cell lines, and analysed genetic a...
Cancer geneticsCancer genomics
10.1038/S41586-020-03114-6
ISSN:0028-0836
INPP5A phosphatase is a synthetic lethal target in GNAQ and GNA11-mutant melanomas
Ahmed M. O. Elbatsh•Ali Amin-Mansour•Anne Haberkorn•Claudia Textor•Nicolas Ebel等 22 人
Nature Cancer
2024
•2024/1/17
•00 p.1-19
Activating mutations in GNAQ/GNA11 occur in over 90% of uveal melanomas (UMs), the most lethal melanoma subtype; however, targeting these oncogenes has proven challenging and inhibiting their downstream effectors show limited clinical efficacy. Here, we performed genome-scale CRISPR screens along wi...
CancerCancer geneticsEye cancer
10.1038/S43018-023-00710-Z
ISSN:2662-1347
Expanding PROTACtable genome universe of E3 ligases
Yuan Liu•Jingwen Yang•Tianlu Wang•Mei Luo•Yamei Chen等 10 人
Nature Communications
2023
•2023/10/16
•Vol.14 No.1 p.1-17
Proteolysis-targeting chimera (PROTAC) and other targeted protein degradation (TPD) molecules that induce degradation by the ubiquitin-proteasome system (UPS) offer new opportunities to engage targets that remain challenging to be inhibited by conventional small molecules. One fundamental element in...
Cancer genomicsComputational biology and bioinformaticsUbiquitin ligases
10.1038/S41467-023-42233-2
ISSN:2041-1723
Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer
Xiaocui Lu•Xiuyun Wang•Zheng Yang•Xusheng Wang•Lin Wang等 21 人
Nature
2026
•2026/6/10
•00 p.1-10
BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerizat...
Targeted therapies
10.1038/S41586-026-10613-5
ISSN:0028-0836
Multiplexed single-cell transcriptional response profiling to define cancer vulnerabilities and therapeutic mechanism of action
James M. McFarland•Brenton R. Paolella•Allison Warren•Kathryn Geiger-Schuller•Tsukasa Shibue等 22 人
Nature Communications
2020
•2020/8/27
•Vol.11 No.1 p.1-15
Assays to study cancer cell responses to pharmacologic or genetic perturbations are typically restricted to using simple phenotypic readouts such as proliferation rate. Information-rich assays, such as gene-expression profiling, have generally not permitted efficient profiling of a given perturbatio...
Cancer genomicsGene expression analysisGene expression profiling
10.1038/S41467-020-17440-W
ISSN:2041-1723
A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population
Qu Yuanyuan•Feng Jinwen•Wu Xiaohui•Bai Lin•Xu Wenhao等 25 人
Nature Communications
2022
•2022/4/19
•Vol.13 No.1 p.1-21
Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of renal cancer. Here we conduct a comprehensive proteogenomic analysis of 232 tumor and adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tumor adjacent tissues, we find that ccRCC shows extensiv...
ProteomicsTumour heterogeneityUrological cancer
10.1038/S41467-022-29577-X
ISSN:2041-1723
Targeting histone H2B acetylated enhanceosomes via p300/CBP degradation in prostate cancer
Jie Luo•Zhixiang Chen•Yuanyuan Qiao•Jean Ching-Yi Tien•Eleanor Young等 29 人
Nature Genetics
2025
•2025/10/3
•00 p.1-14
Prostate cancer is driven by oncogenic transcription factor enhanceosomes comprising chromatin and epigenetic regulators. The lysine acetyltransferases p300 and CREB-binding protein (CBP) are key cofactors that activate enhancers through histone acetylation. Here we identify p300/CBP-mediated multis...
EpigeneticsProstate cancerTargeted therapies
10.1038/S41588-025-02336-6
ISSN:1061-4036
Suppression of NRAS-mutant melanoma growth with NRAS-targeting Antisense Oligonucleotide treatment reveals therapeutically relevant kinase co-dependencies
Valentin Feichtenschlager•Yixuan James Zheng•Tiange Qu•Dasha Hohlova•Ciara Callanan等 17 人
Communications Medicine
2025
•2025/6/5
•Vol.5 No.1 p.1-16
Melanoma is an aggressive form of skin cancer, and patients with NRAS-mutant melanoma face limited treatment options due to the lack of direct NRAS inhibitors. This study explores the utilization of antisense oligonucleotides (ASOs) to directly target NRAS-mRNA for therapeutic approaches. We designe...
Cell signallingMelanomaTargeted therapies
10.1038/S43856-025-00932-5
ISSN:2730-664X
VDAC2 and Bak scarcity in liver mitochondria enables targeting hepatocarcinoma while sparing hepatocytes
Shamim Naghdi•Piyush Mishra•Soumya Sinha Roy•David Weaver•Ludivine Walter等 17 人
Nature Communications
2025
•2025/3/11
•Vol.16 No.1 p.1-20
Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by trunca...
Energy metabolismHepatocellular carcinoma
10.1038/S41467-025-56898-4
ISSN:2041-1723
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
Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma
Xiao Chen•Yinglu Li•Fang Zhu•Xinjing Xu•Brian Estrella等 17 人
Nature Communications
2023
•2023/7/17
•Vol.14 No.1 p.1-17
Interplay between chromatin-associated complexes and modifications critically contribute to the partitioning of epigenome into stable and functionally distinct domains. Yet there is a lack of systematic identification of chromatin crosstalk mechanisms, limiting our understanding of the dynamic trans...
Cancer epigeneticsNon-hodgkin lymphoma
10.1038/S41467-023-39990-5
ISSN:2041-1723
Expanding the human proteome with microproteins and peptideins
Eric W. Deutsch•Leron W. Kok•Jonathan M. Mudge•Cristian F. Valls•Irwin Jungreis等 64 人
Nature
2026
•2026/5/6
•00 p.1-13
A major scientific drive is to characterize the protein-coding genome, which is a primary basis for studying human health. But the fundamental question remains of what has been missed in previous analyses. Over the past decade, the translation of non-canonical open reading frames (ncORFs) has been o...
Evolutionary biologyGene expressionGenetic databasesOpen reading framesProtein databases
10.1038/S41586-026-10459-X
ISSN:0028-0836
BIT: Bayesian Identification of Transcriptional regulators from epigenomics-based query region sets
Zeyu Lu•Lin Xu•Xinlei Wang
Nature Communications
2025
•2025/5/28
•Vol.16 No.1 p.1-17
Transcriptional regulators (TRs) are master controllers of gene expression and play a critical role in both normal tissue development and disease progression. However, existing computational methods for identification of TRs regulating specific biological processes have significant limitations, such...
Computational modelsEpigenomicsSoftwareStatistical methodsTranscription
10.1038/S41467-025-60269-4
ISSN:2041-1723
Target expression is a relevant factor in synthetic lethal screens
Schultz Iman J.•Coelingh Bennink Herjan J. T.
Communications Biology
2022
•2022/8/19
•Vol.5 No.1 p.1-2
CRISPR-Cas9 genome editingTarget identification
10.1038/S42003-022-03746-6
ISSN:2399-3642
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
Deciphering genetic susceptibility to clear cell renal cell carcinoma
Maria Mandelia•Philip J. Law•Charlie Mills•Molly Went•Jayaram Vijayakrishnan等 6 人
Communications Biology
2025
•2025/12/1
0Genome-wide association studies (GWAS) have identified over 60 autosomal risk loci associated with clear cell renal cell carcinoma (ccRCC), yet the functional mechanisms underlying these associations remain largely unclear. To establish connections between risk variants and their target genes, we ap...
Cancer geneticsCancer genomicsEpigeneticsGene regulatory networksRenal cell carcinoma
10.1038/S42003-025-09297-W
ISSN:2399-3642
A single-cell analysis of breast cancer cell lines to study tumour heterogeneity and drug response
Gambardella G.•Viscido G.•Tumaini B.•Isacchi A.•Bosotti R.等 6 人
Nature Communications
2022
•2022/3/31
•Vol.13 No.1 p.1-12
Cancer cells within a tumour have heterogeneous phenotypes and exhibit dynamic plasticity. How to evaluate such heterogeneity and its impact on outcome and drug response is still unclear. Here, we transcriptionally profile 35,276 individual cells from 32 breast cancer cell lines to yield a single ce...
Breast cancerCancer genomicsCancer therapyGene regulatory networksTumour heterogeneity
10.1038/S41467-022-29358-6
ISSN:2041-1723
An integrated functional and clinical genomics approach reveals genes driving aggressive metastatic prostate cancer
Das Rajdeep•Sjöström Martin•Shrestha Raunak•Yogodzinski Christopher•Egusa Emily A.等 18 人
Nature Communications
2021
•2021/7/29
•Vol.12 No.1 p.1-12
Genomic sequencing of thousands of tumors has revealed many genes associated with specific types of cancer. Similarly, large scale CRISPR functional genomics efforts have mapped genes required for cancer cell proliferation or survival in hundreds of cell lines. Despite this, for specific disease sub...
Cancer genomicsProstate cancer
10.1038/S41467-021-24919-7
ISSN:2041-1723
Targeting KRAS4A splicing through the RBM39/DCAF15 pathway inhibits cancer stem cells
Wei-Ching Chen•Minh D. To•Peter M. K. Westcott•Reyno Delrosario•Il-Jin Kim等 12 人
Nature Communications
2021
•2021/7/13
•Vol.12 No.1 p.1-14
The commonly mutated human KRAS oncogene encodes two distinct KRAS4A and KRAS4B proteins generated by differential splicing. We demonstrate here that coordinated regulation of both isoforms through control of splicing is essential for development of Kras mutant tumors. The minor KRAS4A isoform is en...
Cancer geneticsCancer stem cellsTranscription
10.1038/S41467-021-24498-7
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
A genome-wide association study identifies an African-specific locus on chromosome 21q22.12 associated with Burkitt lymphoma risk and survival
Diptavo Dutta•Mateus H. Gouveia•Bryan R. Gorman•Atuahene Adu-Gyamfi•Chia-Han Lee等 49 人
Leukemia
2025
•2025/7/11
•00 p.1-11
Burkitt lymphoma (BL) is a B-cell malignancy that disproportionately affects children in sub-Saharan Africa. We performed a genome-wide association study (GWAS) in a combined set of 800 childhood cases and 3865 controls in East Africa, controlling for age, sex, country, population-specific principal...
Cancer epidemiologyGenetics research
10.1038/S41375-025-02690-8
ISSN:0887-6924
A protein expression atlas on tissue samples and cell lines from cancer patients provides insights into tumor heterogeneity and dependencies
Jun Li•Wei Liu•Kamalika Mojumdar•Hong Kim•Zhicheng Zhou等 14 人
Nature Cancer
2024
•2024/9/3
•00 p.1-17
The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) are foundational resources in cancer research, providing extensive molecular and phenotypic data. However, large-scale proteomic data across various cancer types for these cohorts remain limited. Here, we expand upon our pre...
CancerComputational biology and bioinformaticsProteomic analysis
10.1038/S43018-024-00817-X
ISSN:2662-1347
Integrated cross-study datasets of genetic dependencies in cancer
Clare Pacini•Joshua M. Dempster•Isabella Boyle•Emanuel Gonçalves•Hanna Najgebauer等 14 人
Nature Communications
2021
•2021/3/12
•Vol.12 No.1 p.1-14
CRISPR-Cas9 viability screens are increasingly performed at a genome-wide scale across large panels of cell lines to identify new therapeutic targets for precision cancer therapy. Integrating the datasets resulting from these studies is necessary to adequately represent the heterogeneity of human ca...
Cancer genomicsData integration
10.1038/S41467-021-21898-7
ISSN:2041-1723
The Cancer Surfaceome Atlas integrates genomic, functional and drug response data to identify actionable targets
Hu Zhongyi•Yuan Jiao•Long Meixiao•Jiang Junjie•Zhang Youyou等 15 人
Nature Cancer
2021
•2021/12/13
•00 p.1-17
Cell-surface proteins (SPs) are a rich source of immune and targeted therapies. By systematically integrating single-cell and bulk genomics, functional studies and target actionability, in the present study we comprehensively identify and annotate genes encoding SPs (GESPs) pan-cancer. We characteri...
CancerCancer genomicsCancer therapyTumour immunology
10.1038/S43018-021-00282-W
ISSN:2662-1347
The PENGUIN approach to reconstruct protein interactions at enhancer-promoter regions and its application to prostate cancer
Alexandros Armaos•François Serra•Iker Núñez-Carpintero•Ji-Heui Seo•Sylvan C. Baca等 11 人
Nature Communications
2023
•2023/12/6
•Vol.14 No.1 p.1-17
We introduce Promoter-Enhancer-Guided Interaction Networks (PENGUIN), a method for studying protein-protein interaction (PPI) networks within enhancer-promoter interactions. PENGUIN integrates H3K27ac-HiChIP data with tissue-specific PPIs to define enhancer-promoter PPI networks (EPINs). We validate...
Cancer geneticsGenome informatics
10.1038/S41467-023-43767-1
ISSN:2041-1723
Differential activity of MAPK signalling defines fibroblast subtypes in pancreatic cancer
Lisa Veghini•Davide Pasini•Rui Fang•Pietro Delfino•Dea Filippini等 24 人
Nature Communications
2024
•2024/12/3
•Vol.15 No.1 p.1-20
Fibroblast heterogeneity is increasingly recognised across cancer conditions. Given their important contribution to disease progression, mapping fibroblasts’ heterogeneity is critical to devise effective anti-cancer therapies. Cancer-associated fibroblasts (CAFs) represent the most abundant cell pop...
Cancer microenvironmentPancreatic cancer
10.1038/S41467-024-54975-8
ISSN:2041-1723
Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies
Li Yan•Xu Chen•Wang Bing•Xu Fujiang•Ma Fahan等 25 人
Nature Communications
2022
•2022/9/29
•Vol.13 No.1 p.1-26
Chemotherapy and targeted therapy are the major treatments for gastric cancer (GC), but drug resistance limits its effectiveness. Here, we profile the proteome of 206 tumor tissues from patients with GC undergoing either chemotherapy or anti-HER2-based therapy. Proteome-based classification reveals ...
Cancer therapeutic resistanceGastric cancer
10.1038/S41467-022-33282-0
ISSN:2041-1723
Vitamin B2 metabolism promotes FSP1 stability to prevent ferroptosis
Kirandeep K. Deol•Cynthia A. Harris•Sydney J. Tomlinson•Colin J. Delaney•Amr Al-Farhan等 9 人
Nature Structural & Molecular Biology
2026
•2026/3/13
•Vol.33 No.3 p.525-536
Ferroptosis, a regulated form of cell death driven by excessive lipid peroxidation, has emerged as a promising therapeutic target in cancer. Ferroptosis suppressor protein 1 (FSP1) is a critical regulator of ferroptosis resistance, yet the mechanisms controlling its expression and stability remain m...
Cell deathHigh-throughput screeningMolecular biologyProteolysis
10.1038/S41594-026-01759-X
ISSN:1545-9993
Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer
Li Jing•Ohmura Shunya•Marchetto Aruna•Orth Martin F.•Imle Roland等 23 人
Nature Communications
2021
•2021/9/16
•Vol.12 No.1 p.1-12
Chromosomal instability (CIN) is a hallmark of cancer1. Yet, many childhood cancers, such as Ewing sarcoma (EwS), feature remarkably ‘silent’ genomes with minimal CIN2. Here, we show in the EwS model how uncoupling of mitosis and cytokinesis via targeting protein regulator of cytokinesis 1 (PRC1) or...
Bone cancerPaediatric cancerPredictive markersTumour biomarkers
10.1038/S41467-021-25553-Z
ISSN:2041-1723
Multi-omics and single cell characterization of cancer immunosenescence landscape
Qiuxia Wei•Ruizhi Chen•Xue He•Yanan Qu•Changjian Yan等 23 人
Scientific Data
2024
•2024/7/7
•Vol.11 No.1 p.1-16
Cellular senescence (CS) is closely related to tumor progression. However, the studies about CS genes across human cancers have not explored the relationship between cancer senescence signature and telomere length. Additionally, single-cell analyses have not revealed the evolutionary trends of malig...
Cancer microenvironmentRisk factors
10.1038/S41597-024-03562-Z
ISSN:2052-4463
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
Targeting IRF1-TRIM21 axis enhances anti-tumor immunity by promoting ubiquitin-mediated degradation of FGL1 in non-small cell lung cancer
Yuchen Zhang•Pingjing Zhou•Yifan Guo•Hongyu Zhang•Guangyin Zhao等 10 人
Communications Biology
2026
•2026/4/22
0Immunotherapy has emerged as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC), but over half of patients fail to benefit, largely due to tumor heterogeneity and a complex tumor microenvironment. Here, we demonstrate that fibrinogen-like protein 1 (FGL1), a recentl...
Non-small-cell lung cancerUbiquitylation
10.1038/S42003-026-10070-W
ISSN:2399-3642
Assigning functionality to cysteines by base editing of cancer dependency genes
Haoxin Li•Tiantai Ma•Jarrett R. Remsberg•Sang Joon Won•Kristen E. DeMeester等 16 人
Nature Chemical Biology
2023
•2023/10/2
•00 p.1-11
Covalent chemistry represents an attractive strategy for expanding the ligandability of the proteome, and chemical proteomics has revealed numerous electrophile-reactive cysteines on diverse human proteins. Determining which of these covalent binding events affect protein function, however, remains ...
CancerChemical toolsGeneticsProteomics
10.1038/S41589-023-01428-W
ISSN:1552-4450
Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal-like cancers
Tim Arnoldus•Alex van Vliet•Onno B. Bleijerveld•Adriaan F. H. de Groot•Qinglin Piao等 19 人
Nature Genetics
2025
•2025/7/4
•Vol.57 No.7 p.1659-1671
Synthetic lethal interactions (SLIs) based on genomic alterations in cancer have been therapeutically explored. We investigated the SLI space as a function of differential RNA expression in cancer and normal tissue. Computational analyses of functional genomic and gene expression resources uncovered...
Cancer therapyChemical biologyData miningFunctional genomicsGene expression
10.1038/S41588-025-02221-2
ISSN:1061-4036
Discovering functional evolutionary dependencies in human cancers
Marco Mina•Arvind Iyer•Daniele Tavernari•Franck Raynaud•Giovanni Ciriello
Nature Genetics
2020
•2020/9/28
•Vol.52 No.11 p.1198-1207
Cancer cells retain genomic alterations that provide a selective advantage. The prediction and validation of advantageous alterations are major challenges in cancer genomics. Moreover, it is crucial to understand how the coexistence of specific alterations alters response to genetic and therapeutic ...
CancerComputational biology and bioinformaticsGenome informaticsHigh-throughput screeningOncogenes
10.1038/S41588-020-0703-5
ISSN:1061-4036
3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression
Katelyn L. Mortenson•Courtney Dawes•Emily R. Wilson•Nathan E. Patchen•Hailey E. Johnson等 10 人
Nature Communications
2024
•2024/7/20
•Vol.15 No.1 p.1-15
Cancer genomes are composed of many complex structural alterations on chromosomes and extrachromosomal DNA (ecDNA), making it difficult to identify non-coding enhancer regions that are hijacked to activate oncogene expression. Here, we describe a 3D genomics-based analysis called HAPI (Highly Active...
Cancer genomicsOncogenes
10.1038/S41467-024-50387-W
ISSN:2041-1723
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
The origins and genetic interactions of KRAS mutations are allele- and tissue-specific
Joshua H. Cook•Giorgio E. M. Melloni•Doga C. Gulhan•Peter J. Park•Kevin M. Haigis
Nature Communications
2021
•2021/3/22
•Vol.12 No.1 p.1-14
Mutational activation of KRAS promotes the initiation and progression of cancers, especially in the colorectum, pancreas, lung, and blood plasma, with varying prevalence of specific activating missense mutations. Although epidemiological studies connect specific alleles to clinical outcomes, the mec...
Cancer geneticsComputational biology and bioinformatics
10.1038/S41467-021-22125-Z
ISSN:2041-1723
Functional analysis of cancer-associated germline risk variants
Laura N. Kellman•Poornima H. Neela•Suhas Srinivasan•Zurab Siprashvili•Ronald L. Shanderson等 27 人
Nature Genetics
2025
•2025/2/17
•Vol.57 No.3 p.718-728
Single-nucleotide variants (SNVs) in regulatory DNA are linked to inherited cancer risk. Massively parallel reporter assays of 4,041 SNVs linked to 13 neoplasms comprising >90% of human malignancies were performed in pertinent primary human cell types and then integrated with matching chromatin a...
CancerFunctional genomics
10.1038/S41588-024-02070-5
ISSN:1061-4036
Few-shot learning creates predictive models of drug response that translate from high-throughput screens to individual patients
Jianzhu Ma•Samson H. Fong•Yunan Luo•Christopher J. Bakkenist•John Paul Shen等 11 人
Nature Cancer
2021
•2021/1/25
•Vol.2 No.2 p.233-244
Cell-line screens create expansive datasets for learning predictive markers of drug response, but these models do not readily translate to the clinic with its diverse contexts and limited data. In the present study, we apply a recently developed technique, few-shot machine learning, to train a versa...
CancerMachine learningSystems biology
10.1038/S43018-020-00169-2
ISSN:2662-1347
Phase separation of FSP1 promotes ferroptosis
Toshitaka Nakamura•Clara Hipp•André Santos Dias Mourão•Jan Borggräfe•Maceler Aldrovandi等 13 人
Nature
2023
•2023/6/28
•00 p.1-7
Ferroptosis is evolving as a highly promising approach to combat difficult-to-treat tumour entities including therapy-refractory and dedifferentiating cancers1–3. Recently, ferroptosis suppressor protein-1 (FSP1), along with extramitochondrial ubiquinone or exogenous vitamin K and NAD(P)H/H+ as an e...
Cell deathDrug screeningOxidoreductases
10.1038/S41586-023-06255-6
ISSN:0028-0836
DKC1 promotes colorectal cancer progression and therapy resistance by dysregulating sphingolipid biosynthesis
Umar K. Khan•Ayush Goel•Shivansh Nigam•Nazia Chaudhary•Ayush Praveen等 19 人
Nature Communications
2026
•2026/5/18
•Vol.17 No.1 p.44060
DKC1, a key coordinator of RNA modification and telomerase activity, has been implicated in colorectal cancer (CRC), yet its role in disease pathogenesis remains incompletely understood. We show that DKC1 drives CRC by promoting cell cycle progression, suppressing apoptosis, conferring stemness and ...
Cancer metabolismColon cancer
10.1038/S41467-026-72800-2
ISSN:2041-1723
CENPF (+) cancer cells promote malignant progression of early-stage TP53 mutant lung adenocarcinoma
Yanlu Xiong•Jie Lei•Miaomiao Wen•Yongfu Ma•Jinbo Zhao等 19 人
Oncogenesis
2025
•2025/3/5
•Vol.14 No.1 p.1-15
The prevention and precise treatment of early-stage lung adenocarcinoma (LUAD) characterized by small nodules (stage IA) remains a significant challenge for clinicians, which is due largely to the limited understanding of the oncogenic mechanisms spanning from preneoplasia to invasive adenocarcinoma...
Non-small-cell lung cancerOncogenes
10.1038/S41389-025-00546-5
ISSN:2157-9024
Network-based assessment of HDAC6 activity predicts preclinical and clinical responses to the HDAC6 inhibitor ricolinostat in breast cancer
Zeleke Tizita Z.•Pan Qingfei•Chiuzan Codruta•Onishi Maika•Li Yuxin等 26 人
Nature Cancer
2022
•2022/12/30
•Vol.4 No.2 p.257-275
Inhibiting individual histone deacetylase (HDAC) is emerging as well-tolerated anticancer strategy compared with pan-HDAC inhibitors. Through preclinical studies, we demonstrated that the sensitivity to the leading HDAC6 inhibitor (HDAC6i) ricolinstat can be predicted by a computational network-base...
Breast cancerTargeted therapiesTumour biomarkers
10.1038/S43018-022-00489-5
ISSN:2662-1347
PHIP suppresses NuRD to enable the growth of SWI/SNF-mutant cancers
Hayden A. Malone•Jacquelyn A. Myers•Emma G. Gruss•Marc A. Morgan•Jake D. Friske等 17 人
Nature Communications
2026
•2026/4/7
•Vol.17 No.1 p.28770
SWI/SNF chromatin remodeling complexes are perturbed in 20% of all cancers and in several developmental disorders, yet the mechanisms by which these mutations dysregulate transcription and drive disease are poorly understood. To both elucidate these mechanisms and identify vulnerabilities caused by ...
Chromatin remodellingEpigeneticsMechanisms of diseasePaediatric cancerTumour-suppressor proteins
10.1038/S41467-026-70699-3
ISSN:2041-1723
A STUB1–CHIC2 complex inhibits CD8+ T cells to restrain tumor immunity
Martin W. LaFleur•Lauren E. Milling•Priyamvada Prathima•Vivian Li•Ashlyn M. Lemmen等 15 人
Nature Immunology
2025
•2025/8/12
•00 p.1-12
In vivo CRISPR screens in CD8+ T cells have previously uncovered targets for cancer immunotherapy; however, a minority of the genome has been individually annotated, suggesting that additional regulators remain to be discovered. Here we assessed 899 genes in CD8+ T cells responding to murine melanom...
Gene regulation in immune cellsTumour immunology
10.1038/S41590-025-02231-6
ISSN:1529-2908
Indisulam targets RNA splicing and metabolism to serve as a therapeutic strategy for high-risk neuroblastoma
Nijhuis Anke•Sikka Arti•Yogev Orli•Herendi Lili•Balcells Cristina等 22 人
Nature Communications
2022
•2022/3/16
•Vol.13 No.1 p.1-16
Neuroblastoma is the most common paediatric solid tumour and prognosis remains poor for high-risk cases despite the use of multimodal treatment. Analysis of public drug sensitivity data showed neuroblastoma lines to be sensitive to indisulam, a molecular glue that selectively targets RNA splicing fa...
Cancer metabolismPharmacodynamicsTargeted therapies
10.1038/S41467-022-28907-3
ISSN:2041-1723
Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data
Chen Junyi•Wang Xiaoying•Ma Anjun•Wang Qi-En•Liu Bingqiang等 8 人
Nature Communications
2022
•2022/10/30
•Vol.13 No.1 p.1-13
Drug screening data from massive bulk gene expression databases can be analyzed to determine the optimal clinical application of cancer drugs. The growing amount of single-cell RNA sequencing (scRNA-seq) data also provides insights into improving therapeutic effectiveness by helping to study the het...
Cancer genomicsCancer therapyPredictive markersSoftware
10.1038/S41467-022-34277-7
ISSN:2041-1723
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation
Apoorva Uboveja•Baixue Yang•Raquel Buj•Amandine Amalric•Hui Wang等 39 人
Nature
2026
•2026/5/27
•00 p.1-11
Homologous recombination (HR) deficiency increases sensitivity to DNA-damaging agents that are commonly used to treat cancer1. In HR-proficient cancers, the metabolic mechanisms that drive response or resistance to DNA-damaging agents remain unclear. Here we have identified that depletion of α-ketog...
AcetylationCancer metabolismHomologous recombination
10.1038/S41586-026-10584-7
ISSN:0028-0836
Pooled genetic screens to identify vulnerabilities in TERT-promoter-mutant glioblastoma
Kevin J. Tu•Connor E. Stewart•Peter G. Hendrickson•Joshua A. Regal•So Young Kim等 8 人
Oncogene
2023
•2023/9/23
•00 p.1-13
Pooled genetic screens represent a powerful approach to identify vulnerabilities in cancer. Here we used pooled CRISPR/Cas9-based approaches to identify vulnerabilities associated with telomerase reverse transcriptase (TERT) promoter mutations (TPMs) found in >80% of glioblastomas. We first devel...
Cancer geneticsCNS cancer
10.1038/S41388-023-02845-W
ISSN:0950-9232
Identification of breast cancer subtypes and drug response prediction through forward and reverse translation
Julie Karam•Paul A. Rejto•Jadwiga Renata Bienkowska•Xinmeng Jasmine Mu•Whijae Roh
Npj Precision Oncology
2025
•2025/7/31
•Vol.9 No.1 p.1-10
Breast cancer (BRCA) is the most frequently diagnosed cancer among women and the second leading cause of cancer-related mortality worldwide. Biomarkers that predict therapeutic response can guide the choice of treatment modality and improve patient outcomes. We applied the bulk gene expression decon...
Breast cancerCancerCancer genomicsCancer modelsCancer therapyOncology+1
10.1038/S41698-025-01062-W
ISSN:2397-768X
Development and implementation of the SUM breast cancer cell line functional genomics knowledge base
Stephen P. Ethier•Stephen T. Guest•Elizabeth Garrett-Mayer•Kent Armeson•Robert C. Wilson等 9 人
Npj Breast Cancer
2020
•2020/7/21
•Vol.6 No.1 p.1-14
Several years ago, the SUM panel of human breast cancer cell lines was developed, and these cell lines have been distributed to hundreds of labs worldwide. Our lab and others have developed extensive omics data sets from these cells. More recently, we performed genome-scale shRNA essentiality screen...
Cancer genomicsCell signalling
10.1038/S41523-020-0173-Z
ISSN:2374-4677
Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers
Mariluz Soula•Ross A. Weber•Omkar Zilka•Hanan Alwaseem•Konnor La等 10 人
Nature Chemical Biology
2020
•2020/8/10
•Vol.16 No.12 p.1351-1360
Cancer cells rewire their metabolism and rely on endogenous antioxidants to mitigate lethal oxidative damage to lipids. However, the metabolic processes that modulate the response to lipid peroxidation are poorly defined. Using genetic screens, we compared metabolic genes essential for proliferation...
CancerCell deathMembrane lipidsMetabolomics
10.1038/S41589-020-0613-Y
ISSN:1552-4450
Non-canonical MLL1 activity regulates centromeric phase separation and genome stability
Liang Sha•Zi Yang•Sojin An•Wentao Yang•Sungmin Kim等 13 人
Nature Cell Biology
2023
•2023/11/9
•Vol.25 No.11 p.1637-1649
Epigenetic dysregulation is a prominent feature in cancer, as exemplified by frequent mutations in chromatin regulators, including the MLL/KMT2 family of histone methyltransferases. Although MLL1/KMT2A activity on H3K4 methylation is well documented, their non-canonical activities remain mostly unex...
CentromeresGenomic instabilityHepatocellular carcinomaMitosis
10.1038/S41556-023-01270-1
ISSN:1465-7392
Bio-primed machine learning to enhance discovery of relevant biomarkers
David M. Henke•Alexander Renwick•Joseph R. Zoeller•Jitendra K. Meena•Nicholas J. Neill等 9 人
Npj Precision Oncology
2025
•2025/2/6
•Vol.9 No.1 p.1-10
Precision medicine relies on identifying reliable biomarkers for gene dependencies to tailor individualized therapeutic strategies. The advent of high-throughput technologies presents unprecedented opportunities to explore molecular disease mechanisms but also challenges due to high dimensionality a...
BiomarkersCancerComputational biology and bioinformaticsMolecular medicineOncology
10.1038/S41698-025-00825-9
ISSN:2397-768X
The transcriptomic architecture of common cancers reflects synthetic lethal interactions
Syed Haider•Rachel Brough•Santiago Madera•Jacopo Iacovacci•Aditi Gulati等 10 人
Nature Genetics
2025
•2025/3/3
•Vol.57 No.3 p.522-529
To maintain cell fitness, deleterious genetic alterations are buffered by compensatory changes in additional genes. In cancer, buffering processes could be targeted by synthetic lethality. However, despite the large-scale identification of synthetic lethal effects in preclinical models, evidence tha...
CancerComputational biology and bioinformatics
10.1038/S41588-025-02108-2
ISSN:1061-4036
Context-dependent synthetic lethality — an emerging precision therapeutic approach
Liang Chang•Katharin Shaw•Francisca Vazquez•William R. Sellers
Nature Reviews Cancer
2026
•2026/4/23
•00 p.1-21
Context-dependent synthetic lethality offers a promising strategy for expanding the scope of precision oncology beyond direct oncogene inhibition. We describe various genetic contexts that produce cancer-intrinsic vulnerabilities and consequent synthetic lethal opportunities. We also identify common...
Cancer geneticsCancer genomicsCancer therapy
10.1038/S41568-026-00929-9
ISSN:1474-175X
Large-scale drug sensitivity, gene dependency, and proteogenomic analyses of telomere maintenance mechanisms in cancer cells
Yangxiu Wu•Zhaoxiang Cai•Dale Cross•Jane R. Noble•Kelsy Prest等 22 人
Nature Communications
2025
•2025/12/23
•Vol.16 No.1 p.113370
Replicative immortality is a hallmark of cancer, driven by the activation of telomere maintenance mechanisms, that is yet to be therapeutically exploited. To expedite discoveries that will enable the development of therapeutics that target telomere maintenance mechanisms, this study provides a resou...
Cancer genomicsCancer modelsOncogenesTelomeresTumour biomarkers
10.1038/S41467-025-67190-W
ISSN:2041-1723
SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry
Decaesteker Bieke•Louwagie Amber•Loontiens Siebe•De Vloed Fanny•Bekaert Sarah-Lee等 30 人
Nature Communications
2023
•2023/3/7
•Vol.14 No.1 p.1-16
The pediatric extra-cranial tumor neuroblastoma displays a low mutational burden while recurrent copy number alterations are present in most high-risk cases. Here, we identify SOX11 as a dependency transcription factor in adrenergic neuroblastoma based on recurrent chromosome 2p focal gains and ampl...
Cancer epigeneticsOncogenesPaediatric cancer
10.1038/S41467-023-36735-2
ISSN:2041-1723
A T cell resilience model associated with response to immunotherapy in multiple tumor types
Zhang Yu•Trang Vu•Palmer Douglas C.•Kishton Rigel J.•Gong Lanqi等 17 人
Nature Medicine
2022
•2022/5/2
•00 p.1-11
Despite breakthroughs in cancer immunotherapy, most tumor-reactive T cells cannot persist in solid tumors due to an immunosuppressive environment. We developed Tres (tumor-resilient T cell), a computational model utilizing single-cell transcriptomic data to identify signatures of T cells that are re...
Cancer immunotherapyComputational biology and bioinformaticsPredictive markersT cells
10.1038/S41591-022-01799-Y
ISSN:1078-8956
Targeting chromosomally unstable tumors with a selective KIF18A inhibitor
Aaron F. Phillips•Rumin Zhang•Mia Jaffe•Ryan Schulz•Marysol Chu Carty等 21 人
Nature Communications
2025
•2025/1/2
•Vol.16 No.1 p.1-20
Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrati...
CancerDrug developmentMechanisms of disease
10.1038/S41467-024-55300-Z
ISSN:2041-1723
Charting cell-type-specific positive genetic interaction at single-cell resolution for lung adenocarcinoma
Bo Chen•Mingyue Liu•Qi Dong•Chen Lv•Kaidong Liu等 11 人
Npj Precision Oncology
2026
•2026/2/18
•Vol.10 No.1 p.1370
Genetic interactions (GIs) drive carcinogenesis and treatment resistance via non-additive phenotypic effects between genes. Traditional bulk-based methods fail to capture cell-type-specific interactions in heterogeneous tumors like lung adenocarcinoma (LUAD), limiting precision oncology. Resolving c...
Cancer genomicsComputational biology and bioinformaticsTumour biomarkers
10.1038/S41698-026-01328-X
ISSN:2397-768X
UbiDash: A UPS proteomic atlas for tissue-aware degrader design
Tania J. González-Robles•Paul Sastourné•Marisa Triola•Maha Khan•Áron Bartha等 11 人
Cell Death & Differentiation
2026
•2026/7/10
•00 p.1-10
Targeted protein degradation repurposes endogenous E3 ubiquitin ligases to eliminate disease-driving proteins, yet the ligase toolkit deployed clinically remains narrow and largely tissue-agnostic. To support rational expansion of this toolkit, we built a harmonized pan-tissue proteomic atlas of the...
CancerCancer geneticsProteomicsSmall molecules
10.1038/S41418-026-01791-W
ISSN:1350-9047
Zeb1 mediates EMT/plasticity-associated ferroptosis sensitivity in cancer cells by regulating lipogenic enzyme expression and phospholipid composition
Annemarie Schwab•Zhigang Rao•Jie Zhang•André Gollowitzer•Katharina Siebenkäs等 24 人
Nature Cell Biology
2024
•2024/7/15
•00 p.1-12
Therapy resistance and metastasis, the most fatal steps in cancer, are often triggered by a (partial) activation of the epithelial–mesenchymal transition (EMT) programme. A mesenchymal phenotype predisposes to ferroptosis, a cell death pathway exerted by an iron and oxygen-radical-mediated peroxidat...
Cell deathEpithelial–mesenchymal transitionPhospholipids
10.1038/S41556-024-01464-1
ISSN:1465-7392
DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas
Melissa A. Hopper•Abigail R. Dropik•Janek S. Walker•Joseph P. Novak•Miranda S. Laverty等 21 人
Blood Cancer Journal
2024
•2024/10/9
•Vol.14 No.1 p.1-10
This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expr...
B-cell lymphomaCancer genomicsOncogenes
10.1038/S41408-024-01145-0
ISSN:2044-5385
Proline rich 11 ( PRR11 ) overexpression amplifies PI3K signaling and promotes antiestrogen resistance in breast cancer
Kyung-min Lee•Angel L. Guerrero-Zotano•Alberto Servetto•Dhivya R. Sudhan•Chang-Ching Lin等 16 人
Nature Communications
2020
•2020/10/30
•Vol.11 No.1 p.1-15
The 17q23 amplicon is associated with poor outcome in ER+ breast cancers, but the causal genes to endocrine resistance in this amplicon are unclear. Here, we interrogate transcriptome data from primary breast tumors and find that among genes in 17q23, PRR11 is a key gene associated with a poor respo...
Breast cancerCancer therapeutic resistance
10.1038/S41467-020-19291-X
ISSN:2041-1723
BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma
Laubscher Dominik•Gryder Berkley E.•Sunkel Benjamin D.•Andresson Thorkell•Wachtel Marco等 21 人
Nature Communications
2021
•2021/11/26
•Vol.12 No.1 p.1-16
Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype is characterized by t(2;13) or t(1;13) translocations encoding for PAX3- or PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). The f...
EpigeneticsPaediatric cancer
10.1038/S41467-021-27176-W
ISSN:2041-1723
SMARCA4/2 loss reduces BCL-xL expression and confers a druggable MCL1 dependency in cancer
Jialin Jiang•Xianbing Zhu•Zheng Fu•Minyan Lao•Azadeh Arabzadeh等 12 人
Npj Precision Oncology
2026
•2026/3/10
0SMARCA4 (BRG1) and SMARCA2 (BRM) are the mutually exclusive ATPase subunits of the SWI/SNF chromatin remodeling complexes, often altered in cancers. Concurrent loss of SMARCA4/2 is found in some aggressive cancer types, including small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), a rare...
CancerCell biologyOncology
10.1038/S41698-026-01350-Z
ISSN:2397-768X