Nature Reviews Cancer最新文献

The sleeping threat: targeting cancer dormancy to transform metastasis therapy. 睡眠威胁：针对癌症休眠转变转移治疗。

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2026-04-24 DOI: 10.1038/s41568-026-00928-w

Julio A Aguirre-Ghiso,Jose Javier Bravo-Cordero,Wenjun Guo,Gregoire Lauvau,Maria Soledad Sosa

{"title":"The sleeping threat: targeting cancer dormancy to transform metastasis therapy.","authors":"Julio A Aguirre-Ghiso,Jose Javier Bravo-Cordero,Wenjun Guo,Gregoire Lauvau,Maria Soledad Sosa","doi":"10.1038/s41568-026-00928-w","DOIUrl":"https://doi.org/10.1038/s41568-026-00928-w","url":null,"abstract":"Metastatic cancer cell dormancy, wherein disseminated cancer cells (DCCs) persist in a quiescent state before reactivating to fuel metastasis, has emerged as a critical determinant of cancer relapse. In this Review, we synthesize recent advances in understanding the microenvironmental drivers of dormancy, including the role of niche-derived signals and extracellular matrix composition in maintaining DCC quiescence, as well as the epigenetic and transcriptional programmes, and chromatin remodelling that enforce and sustain dormancy. We also cover the mechanisms by which dormant DCCs evade immune surveillance, highlighting both innate and adaptive immune interactions, and the strategies tumours use to escape immune-mediated clearance. Although most data come from solid cancers, we also examine the biology of residual cells in haematologic malignancies that share key dormancy and relapse mechanisms with solid tumours. We also discuss how, despite these mechanistic insights, clinical translation remains limited, as available biomarkers or therapies targeting dormancy have yet to be effectively implemented. We conclude that by outlining the challenges and opportunities for leveraging dormancy biology, we may be able to prevent metastatic recurrence and improve patient outcomes.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"9 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739024","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

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 78.5 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":"https://doi.org/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.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"69 1","pages":""},"PeriodicalIF":78.5,"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 78.5 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":"https://doi.org/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.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 1","pages":""},"PeriodicalIF":78.5,"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 78.5 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 78.5 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

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 78.5 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

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 78.5 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 78.5 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":"https://doi.org/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.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"1 1","pages":""},"PeriodicalIF":78.5,"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 78.5 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":"https://doi.org/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.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"36 1 1","pages":""},"PeriodicalIF":78.5,"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