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Re-envisioning genetic predisposition to childhood and adolescent cancers 重新设想儿童和青少年癌症的遗传易感性
IF 78.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-12-03 DOI: 10.1038/s41568-024-00775-7
Christian P. Kratz
{"title":"Re-envisioning genetic predisposition to childhood and adolescent cancers","authors":"Christian P. Kratz","doi":"10.1038/s41568-024-00775-7","DOIUrl":"https://doi.org/10.1038/s41568-024-00775-7","url":null,"abstract":"<p>Although cancer is rare in children and adolescents, it remains a leading cause of death within this age range, and genetic predisposition is the main known risk factor. Since the discovery of retinoblastoma-predisposing <i>RB1</i> pathogenic germline variants in 1985, several additional high-penetrance cancer predisposition genes (CPGs) have been identified. Although few clinically recognizable genetic conditions display moderate cancer phenotypes, burden testing has revealed low-to-moderate penetrance CPGs. In addition to germline pathogenic variants in CPGs, postzygotic somatic mosaic CPG pathogenic variants acquired during embryonic development are increasingly recognized as factors that predispose children and adolescents to malignancies. Genome-wide association studies of various childhood and adolescent cancer types have identified some common low-risk cancer susceptibility alleles. Although the clinical utility of polygenic risk scores is currently limited in children and adolescents, polygenic risk scores developed for adults can predict subsequent cancer risks in childhood and adolescent cancer survivors. In this Review, I describe our current knowledge of genetic predisposition to childhood and adolescent cancers. Survival rates in children and adolescents with cancer and CPGs are often poor, necessitating better integration of genomic testing into clinical care to improve cancer prevention, surveillance and therapies.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"12 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760481","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
Lactate gives a sour taste 乳酸盐有酸味
IF 72.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-12-03 DOI: 10.1038/s41568-024-00783-7
Daniela Senft
{"title":"Lactate gives a sour taste","authors":"Daniela Senft","doi":"10.1038/s41568-024-00783-7","DOIUrl":"10.1038/s41568-024-00783-7","url":null,"abstract":"Wang et al. demonstrate that lactate derived from glioblastoma stem cells, microglia and macrophages drives histone lactylation, activating immunosuppressive transcriptional programs and upregulating CD47, to suppress phagocytosis.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 1","pages":"5-5"},"PeriodicalIF":72.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760510","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
Identifying memory genes in cancer drug tolerance 识别癌症药物耐受的记忆基因
IF 78.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-12-02 DOI: 10.1038/s41568-024-00780-w
Shaon Chakrabarti
{"title":"Identifying memory genes in cancer drug tolerance","authors":"Shaon Chakrabarti","doi":"10.1038/s41568-024-00780-w","DOIUrl":"https://doi.org/10.1038/s41568-024-00780-w","url":null,"abstract":"In this Journal Club, Chakrabarti discusses a method to dissect the molecular architecture of inheritable gene expression (memory) states that mark cells that transition into drug-tolerant persister cells in melanoma.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"132 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758190","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
Androgen receptor signalling in non-prostatic malignancies: challenges and opportunities 非前列腺恶性肿瘤中的雄激素受体信号：挑战与机遇
IF 78.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-11-25 DOI: 10.1038/s41568-024-00772-w
G. Paolo Dotto, An Buckinx, Berna C. Özdemir, Christian Simon
{"title":"Androgen receptor signalling in non-prostatic malignancies: challenges and opportunities","authors":"G. Paolo Dotto, An Buckinx, Berna C. Özdemir, Christian Simon","doi":"10.1038/s41568-024-00772-w","DOIUrl":"https://doi.org/10.1038/s41568-024-00772-w","url":null,"abstract":"<p>The androgen receptor (AR) signalling pathway has been intensively studied in the context of prostate cancer, where androgen deprivation therapy is part of the standard of care for metastatic disease. By contrast, fewer studies have investigated the impact and translational potential of targeting AR in other cancer types where it is also expressed and functional. In this Review, we discuss the current understanding of AR in non-prostatic cancer types and summarize ongoing AR-directed clinical trials. While different androgen levels contribute to sexual dimorphism in cancer, targeting the AR system could benefit both sexes and help overcome resistance to targeted therapies. However, a bimodal function of AR signalling, which suppresses stromal changes associated with the early stages of cancer development, also needs to be considered. Future research is necessary to scrutinize cellular and molecular mechanisms of action of AR in cancer cells and the tumour microenvironment, to develop selective modulators of AR activity, and to identify patients with non-prostatic cancer who might benefit from targeting this pathway. AR-directed manipulation of host immune cells may offer a promising therapeutic approach for many types of cancers.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"238 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696800","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
Chromothripsis in cancer. 癌症中的染色体分裂
IF 72.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-11-15 DOI: 10.1038/s41568-024-00769-5
Milena Simovic-Lorenz, Aurélie Ernst
{"title":"Chromothripsis in cancer.","authors":"Milena Simovic-Lorenz, Aurélie Ernst","doi":"10.1038/s41568-024-00769-5","DOIUrl":"https://doi.org/10.1038/s41568-024-00769-5","url":null,"abstract":"<p><p>Chromothripsis is a mutational phenomenon in which a single catastrophic event generates extensive rearrangements of one or a few chromosomes. This extreme form of genome instability has been detected in 30-50% of cancers. Studies conducted in the past few years have uncovered insights into how chromothripsis arises and deciphered some of the cellular and molecular consequences of chromosome shattering. This Review discusses the defining features of chromothripsis and describes its prevalence across different cancer types as indicated by the manifestations of chromothripsis detected in human cancer samples. The different mechanistic models of chromothripsis, derived from in vitro systems that enable causal inference through experimental manipulation, are discussed in detail. The contribution of chromothripsis to cancer development, the selective advantages that cancer cells might gain from chromothripsis, the evolutionary trajectories of chromothriptic tumours, and the potential vulnerabilities and therapeutic opportunities presented by chromothriptic cells are also highlighted.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":" ","pages":""},"PeriodicalIF":72.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639389","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
Dedicated centres and multinational platforms to improve patient care and address early-onset cancers 建立专门的中心和多国平台，以改善患者护理并解决早发癌症问题
IF 78.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-11-11 DOI: 10.1038/s41568-024-00777-5
Irit Ben-Aharon, Elizabeth Smyth, Anna D. Wagner
{"title":"Dedicated centres and multinational platforms to improve patient care and address early-onset cancers","authors":"Irit Ben-Aharon, Elizabeth Smyth, Anna D. Wagner","doi":"10.1038/s41568-024-00777-5","DOIUrl":"https://doi.org/10.1038/s41568-024-00777-5","url":null,"abstract":"The incidence of early-onset cancers has increased by approximately 80% over the past three decades. These patients have unique needs. For optimal care, designated OncoYoung programs should be created. In addition, multinational platforms with dedicated funding are necessary to investigate the aetiology of early-onset cancers and develop preventive measures. In this Comment, Ben-Aharon et al. advocate for the creation of designated OncoYoung programs to address the unique needs of individuals with early-onset cancer, as well as multinational platforms with dedicated funding to investigate the aetiology of this disease and to develop preventive measures.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"5 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597979","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
Genetic and epigenetic bases of long-term adverse effects of childhood cancer therapy 儿童癌症治疗长期不良影响的遗传学和表观遗传学基础
IF 78.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-11-07 DOI: 10.1038/s41568-024-00768-6
Zhaoming Wang, Jinghui Zhang
{"title":"Genetic and epigenetic bases of long-term adverse effects of childhood cancer therapy","authors":"Zhaoming Wang, Jinghui Zhang","doi":"10.1038/s41568-024-00768-6","DOIUrl":"https://doi.org/10.1038/s41568-024-00768-6","url":null,"abstract":"<p>Over the past decade, genome-scale molecular profiling of large childhood cancer survivorship cohorts has led to unprecedented advances in our understanding of the genetic and epigenetic bases of therapy-related adverse health outcomes in this vulnerable population. To facilitate the integration of knowledge generated from these studies into formulating next-generation precision care for survivors of childhood cancer, we summarize key findings of genetic and epigenetic association studies of long-term therapy-related adverse effects including subsequent neoplasms and cardiomyopathies among others. We also discuss therapy-related genotoxicities including clonal haematopoiesis and DNA methylation, which may underlie accelerated molecular ageing. Finally, we highlight enhanced risk prediction models for survivors of childhood cancer that incorporate both genetic factors and treatment exposures, aiming to achieve enhanced accuracy in predicting risks for this population. These new insights will hopefully inspire future studies that harness both expanding omics resources and evolving data science methodology to accelerate the translation of precision medicine for survivors of childhood cancer.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"5 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594783","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
Developing multiple EGFR-mutant lung cancers 出现多种表皮生长因子受体突变肺癌
IF 72.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-11-06 DOI: 10.1038/s41568-024-00773-9
Daniela Senft
{"title":"Developing multiple EGFR-mutant lung cancers","authors":"Daniela Senft","doi":"10.1038/s41568-024-00773-9","DOIUrl":"10.1038/s41568-024-00773-9","url":null,"abstract":"The occurrence of multiple independent tumours in patients with EGFR-mutant lung cancer was unexplained. A recent study in Nature Cancer identified distinct genetic predisposition mechanisms, including developmental mosaicism and germline EGFR variants, that contribute to the formation of multiple primary tumours.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 12","pages":"826-826"},"PeriodicalIF":72.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588706","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
Fanconi anaemia pathway induces chromosome shattering 范可尼贫血症通路诱导染色体破碎
IF 72.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-11-06 DOI: 10.1038/s41568-024-00774-8
Gabrielle Brewer
{"title":"Fanconi anaemia pathway induces chromosome shattering","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00774-8","DOIUrl":"10.1038/s41568-024-00774-8","url":null,"abstract":"Engel et al. conducted a genetic screen in which they identified the Fanconi anaemia (FA) pathway as a driver of chromothripsis, complex genomic rearrangements and generation of extrachromosomal DNA.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 12","pages":"827-827"},"PeriodicalIF":72.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589120","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
Author Correction: The importance of 3D fibre architecture in cancer and implications for biomaterial model design 作者更正：三维纤维结构在癌症中的重要性及其对生物材料模型设计的影响
IF 72.5 1区 医学
Nature Reviews Cancer Pub Date : 2024-11-04 DOI: 10.1038/s41568-024-00776-6
Jennifer C. Ashworth, Thomas R. Cox
{"title":"Author Correction: The importance of 3D fibre architecture in cancer and implications for biomaterial model design","authors":"Jennifer C. Ashworth,&nbsp;Thomas R. Cox","doi":"10.1038/s41568-024-00776-6","DOIUrl":"10.1038/s41568-024-00776-6","url":null,"abstract":"","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 1","pages":"74-74"},"PeriodicalIF":72.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41568-024-00776-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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