Nature Reviews Cancer最新文献_第7页

Enhancer and metabolic rewiring by KMT2C–COMPASS or KMT2D–COMPASS family loss in cancer creates druggable vulnerabilities 癌症中KMT2C-COMPASS或KMT2D-COMPASS家族缺失导致的增强子和代谢重新布线产生可药物脆弱性。

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2026-04-24 DOI: 10.1038/s41568-026-00919-x

Zibo Zhao, Ali Shilatifard

{"title":"Enhancer and metabolic rewiring by KMT2C–COMPASS or KMT2D–COMPASS family loss in cancer creates druggable vulnerabilities","authors":"Zibo Zhao, Ali Shilatifard","doi":"10.1038/s41568-026-00919-x","DOIUrl":"10.1038/s41568-026-00919-x","url":null,"abstract":"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–COMPASS are particularly critical for differentiation and cell fate specification. Their catalytic subunits, including the histone H3 lysine 4 (H3K4) monomethyltransferases KMT2C (also known as MLL3) and KMT2D (also known as MLL4) and the H3K27-specific demethylase lysine-specific demethylase 6A (KDM6A; also known as UTX), are encoded by some of the most frequently mutated genes across human cancers, particularly epithelial cancers. The multifaceted roles of KMT2C–COMPASS and KMT2D–COMPASS, the variety of KMT2C, KMT2D and KDM6A mutations found across all cancer types, and the tissue-specific impacts of compromised enhancer regulatory function have posed challenges for direct therapeutic targeting. However, KMT2C–COMPASS and KMT2D–COMPASS mutations also create tumour-specific and potentially targetable vulnerabilities. In this Review, we discuss the functional roles of KMT2C–COMPASS and KMT2D–COMPASS and the impact of their mutations on cancer progression. We outline potential therapeutic strategies to exploit vulnerabilities in cancer cells with altered KMT2C–COMPASS or KMT2D–COMPASS activity, including aberrant epigenetic regulatory complex activity, metabolic rewiring, defects in cell-cycle control and DNA repair, and increased immunogenicity. In this Review, Zhao and Shilatifard examine how mutations in components of the KMT2C-containing or KMT2D-containing COMPASS complex drive cancer progression and discuss therapeutic approaches targeting epigenetic, metabolic, immune and DNA repair vulnerabilities arising from this altered COMPASS activity.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"26 6","pages":"437-451"},"PeriodicalIF":66.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Context-dependent synthetic lethality — an emerging precision therapeutic approach 情境依赖性合成致死性——一种新兴的精确治疗方法。

IF 60.7 1区医学

Nature Reviews Cancer Pub Date : 2026-04-23 DOI: 10.1038/s41568-026-00929-9

Liang Chang, Katharin Shaw, Francisca Vazquez, William R. Sellers

{"title":"Context-dependent synthetic lethality — an emerging precision therapeutic approach","authors":"Liang Chang, Katharin Shaw, Francisca Vazquez, William R. Sellers","doi":"10.1038/s41568-026-00929-9","DOIUrl":"10.1038/s41568-026-00929-9","url":null,"abstract":"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 mechanistic themes that underlie synthetic lethality, such as DNA repair defects, loss of functional redundancies, metabolic imbalances and narrow signalling tolerances. Whereas clinical translation has seen success — for example, with inhibitors of poly(ADP-ribose) polymerase (PARP), hypoxia-inducible factor 2 (HIF-2) and Smoothened (SMO), other targets require more nuanced strategies to achieve selectivity. Case studies highlight that therapeutic index, often inferable from functional genomics, is a critical determinant of success and should guide both target prioritization and therapeutic strategy. They also reveal that specific molecular mechanisms underlying the synthetic lethal phenotype can inform the discovery of the optimal therapeutic modality. Finally, we describe emerging approaches for synthetic lethal target discovery and drug development that enable diverse therapeutic strategies. Together, these insights provide a framework for translating synthetic lethality into more selective and durable cancer therapies. In this Review, Chang et al. discuss context-dependent synthetic lethality whereby various genetic contexts produce cancer-intrinsic vulnerabilities and provide a framework that evaluates and considers therapeutic index to enable the translation of synthetic lethality into more selective and durable cancer therapies.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"26 7","pages":"534-554"},"PeriodicalIF":60.7,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer risk in children with congenital anomalies 先天性畸形儿童患癌症的风险。

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2026-04-22 DOI: 10.1038/s41568-026-00932-0

Philip J. Lupo, Sharon E. Plon

引用次数: 0

Advancing AI for multi-omics and clinical data integration in basic and translational cancer research 推进AI在基础和转化癌症研究中的多组学和临床数据整合。

IF 60.7 1区医学

Nature Reviews Cancer Pub Date : 2026-04-21 DOI: 10.1038/s41568-026-00922-2

Fei Liu, Stephan Beck, Lei Yang, Huiyan Luo, Kang Zhang

{"title":"Advancing AI for multi-omics and clinical data integration in basic and translational cancer research","authors":"Fei Liu, Stephan Beck, Lei Yang, Huiyan Luo, Kang Zhang","doi":"10.1038/s41568-026-00922-2","DOIUrl":"10.1038/s41568-026-00922-2","url":null,"abstract":"The extensive heterogeneity of cancer across biological scales necessitates a holistic approach beyond single-analyte methods. Integrating multi-omics data — from genomics to proteomics — with multimodal information, such as clinical records and medical imaging, offers a comprehensive, systems-level view of tumorigenesis. Artificial intelligence (AI) has emerged as the essential technology to decipher these complex, high-dimensional datasets, powering substantial advances in early diagnosis, precise patient stratification, prediction of therapeutic response and the elucidation of mechanisms of drug resistance. To translate these powerful predictive models into practice, explainable AI is critical for building clinical trust and generating novel, testable biological hypotheses. While challenges in data accessibility and model generalizability persist, the field is advancing toward patient-specific digital twins, promising to simulate individual disease trajectories and optimize treatments, thereby heralding a new era of precision oncology. While high-throughput omics have deepened our understanding of tumour complexity, analyses restricted to a single omics layer risk overlooking key dimensions of biological regulation. In this Review, Liu and colleagues highlight how artificial intelligence could be harnessed for integrating multi-omics data to provide patient-specific insights into cancer mechanisms and treatment response.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"26 7","pages":"497-512"},"PeriodicalIF":60.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microbiota and immune-related adverse events in cancer immunotherapy 癌症免疫治疗中的微生物群和免疫相关不良事件。

IF 60.7 1区医学

Nature Reviews Cancer Pub Date : 2026-04-16 DOI: 10.1038/s41568-026-00921-3

Sarah M. Schneider, Christopher Fan, Yinghong Wang, Robert R. Jenq, Stephanie S. Watowich

{"title":"Microbiota and immune-related adverse events in cancer immunotherapy","authors":"Sarah M. Schneider, Christopher Fan, Yinghong Wang, Robert R. Jenq, Stephanie S. Watowich","doi":"10.1038/s41568-026-00921-3","DOIUrl":"10.1038/s41568-026-00921-3","url":null,"abstract":"In response to treatment with immune checkpoint inhibitors (ICIs), patients with cancer can develop immune-related adverse events (irAEs), which are off-target toxicities affecting non-tumour tissues. Development of an irAE can require cessation of ICI treatment and cause additional morbidities, unrelated to cancer. Although the mechanisms that drive irAEs remain largely unknown, thus limiting treatment strategies, emerging evidence implicates tissue microbiomes, particularly in the gastrointestinal tract, lung and skin, as potential mediators. Here we review evidence that supports roles for the microbiome in irAEs. We focus on ICI colitis, a common irAE that has strong association with the gut microbiome. We examine clinical and preclinical studies that shed light on the immune and microbial drivers of ICI colitis and discuss current experimental treatments. By summarizing recent findings, we aim to encourage research into therapies that reduce irAE risk and severity while preserving anti-tumour efficacy of ICI treatment. Immune-related adverse events (irAEs) complicate cancer immunotherapy, necessitating cancer treatment cessation and management of irAEs. In this Progress article, Schneider et al. highlight the role of the microbiome in driving irAE development and progression, particularly immune checkpoint inhibitor-associated colitis, through clinical and preclinical evidence, emphasizing immune and microbial interactions while discussing potential therapeutic strategies to mitigate risks.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"26 7","pages":"480-496"},"PeriodicalIF":60.7,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

vCATCH enables body-wide in vivo drug distribution mapping vCATCH能够绘制体内药物分布图谱。

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2026-04-15 DOI: 10.1038/s41568-026-00931-1

Zhengyuan Pang

引用次数: 0

The versatile interplay between steatotic liver disease and liver cancer 脂肪肝和肝癌之间的多种相互作用。

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2026-04-14 DOI: 10.1038/s41568-026-00918-y

Mohammad Rahbari, Albert Gris-Oliver, Pierluigi Ramadori, David Aicher, Daniela Sia, Nisar P. Malek, Rohit Loomba, Ramon Bataller, Josep M. Llovet, Mathias Heikenwälder

{"title":"The versatile interplay between steatotic liver disease and liver cancer","authors":"Mohammad Rahbari, Albert Gris-Oliver, Pierluigi Ramadori, David Aicher, Daniela Sia, Nisar P. Malek, Rohit Loomba, Ramon Bataller, Josep M. Llovet, Mathias Heikenwälder","doi":"10.1038/s41568-026-00918-y","DOIUrl":"10.1038/s41568-026-00918-y","url":null,"abstract":"Steatotic liver diseases (SLDs), including metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as non-alcoholic fatty liver disease) and alcoholic liver disease, are the leading causes of chronic hepatitis, liver dysfunction, cirrhosis and liver cancer development. Severe manifestations of MASLD and alcoholic liver disease include metabolic dysfunction-associated steatohepatitis (MASH; formerly known as non-alcoholic steatohepatitis) and alcoholic steatohepatitis (ASH) or a combination thereof, termed metabolic dysfunction and alcohol-associated liver disease. While MASH-associated and ASH-associated liver cancers display common histopathological features, the underlying cellular and molecular pathophysiological mechanisms of each are distinct. Recent studies indicate that SLDs encompass previously unrecognized spectra of heterogeneous, metabolic, immunological and genetic diseases that, in combination with lifestyle measures and individual patient comorbidities, affect disease pathogenesis and therapy response. Here, we review the current knowledge of the molecular, genetic and cellular mechanisms underlying the transition of MASH or ASH to liver cancer as well as novel developments in liver cancer risk assessment in SLDs. We further discuss possible obstacles of differential diagnosis and outline current developments in the therapeutic management of both MASH-related and ASH-related liver cancer. Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease (ALD) are drivers of liver cancer, promoting its development through chronic liver injury and inflammation. In this Review, Rahbari et al. highlight the distinct pathophysiological mechanisms of progression and therapeutic advancements for MASLD and ALD, emphasizing the need for more tailored approaches to manage these complex diseases and their cancer risks.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"26 6","pages":"415-436"},"PeriodicalIF":66.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rethinking ovarian cancer III: the past decade and future directions 重新思考卵巢癌III：过去的十年和未来的方向。

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2026-04-13 DOI: 10.1038/s41568-026-00916-0

Frances R. Balkwill, Céline M. Laumont, Nikki Burdett, Olivia Le Saux, Dale W. Garsed, Whitney R. Grither, Anke M. Nijhuis, Maria S. Recouvreux, Ziqi Kang, Rugang Zhang, Katherine B. Chiappinelli, Jason S. Lee, Denarda Dangaj Laniti, Iain McNeish, Ahmed A. Ahmed, Robert Rottapel, Jose R. Conejo-Garcia, Kunle Odunsi, Paul D. P. Pharoah, Dmitriy Zamarin, Charles A. Ishak, Christina Fotopoulou, Ronald J. Buckanovich, Intidhar Labidi-Galy, James D. Brenton, Ernst Lengyel, David P. Cook, Sophia H. L. George, Stephanie Lheureux, Ronny Drapkin, Kenneth P. Nephew, Sarah Adams, Shailja Pathania, Brad H. Nelson, Anniina Färkkilä, Katherine Fuh, Benjamin G. Neel, David D. Bowtell

{"title":"Rethinking ovarian cancer III: the past decade and future directions","authors":"Frances R. Balkwill, Céline M. Laumont, Nikki Burdett, Olivia Le Saux, Dale W. Garsed, Whitney R. Grither, Anke M. Nijhuis, Maria S. Recouvreux, Ziqi Kang, Rugang Zhang, Katherine B. Chiappinelli, Jason S. Lee, Denarda Dangaj Laniti, Iain McNeish, Ahmed A. Ahmed, Robert Rottapel, Jose R. Conejo-Garcia, Kunle Odunsi, Paul D. P. Pharoah, Dmitriy Zamarin, Charles A. Ishak, Christina Fotopoulou, Ronald J. Buckanovich, Intidhar Labidi-Galy, James D. Brenton, Ernst Lengyel, David P. Cook, Sophia H. L. George, Stephanie Lheureux, Ronny Drapkin, Kenneth P. Nephew, Sarah Adams, Shailja Pathania, Brad H. Nelson, Anniina Färkkilä, Katherine Fuh, Benjamin G. Neel, David D. Bowtell","doi":"10.1038/s41568-026-00916-0","DOIUrl":"10.1038/s41568-026-00916-0","url":null,"abstract":"Approximately 80% of deaths from ovarian cancer are due to high-grade serous carcinoma (HGSC), which has the highest proportion of BRCA1 or BRCA2 (BRCA1/BRCA2) mutations of any cancer type and is a highly chromosomally unstable disease. Despite the introduction of targeted therapies benefitting some patients with HGSC as well as surgical advances, only 50% of patients will survive more than 5 years, and just 30% of patients who present with advanced disease without BRCA1/BRCA2 mutations will survive this long. This Expert Recommendation is based on discussions among emerging and leading ovarian cancer researchers at the 15th Helene Harris Memorial Trust International Forum on ovarian cancer hosted by Ovarian Cancer Action in October 2024. The meeting considered advances in HGSC research and treatment made over the last decade, current challenges, emerging technologies in prevention, early detection, and treatment, and research priorities for the years ahead. In this Expert Recommendation, Bowtell and colleagues outline progress made over the last decade in the research and treatment of high-grade serous carcinoma as well as current challenges and research priorities for the coming years to reduce incidence and improve patient outcomes.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"26 6","pages":"452-471"},"PeriodicalIF":66.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kill three birds with one stone 一石三鸟。

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2026-04-10 DOI: 10.1038/s41568-026-00930-2

Daniela Senft

引用次数: 0

A fatty competitor in tumour immunity 肿瘤免疫中的脂肪竞争者。

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2026-03-31 DOI: 10.1038/s41568-026-00927-x

Gabrielle Brewer

引用次数: 0