Nature Reviews Cancer最新文献_第7页

Conventional chemotherapy: millions of cures, unresolved therapeutic index 传统化疗：治愈了数百万人，治疗指数仍未确定

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-12-16 DOI: 10.1038/s41568-024-00778-4

Anthony Letai, Hugues de The

{"title":"Conventional chemotherapy: millions of cures, unresolved therapeutic index","authors":"Anthony Letai, Hugues de The","doi":"10.1038/s41568-024-00778-4","DOIUrl":"10.1038/s41568-024-00778-4","url":null,"abstract":"In recent decades, millions of patients with cancer have been cured by chemotherapy alone. By ‘cure’, we mean that patients with cancers that would be fatal if left untreated receive a time-limited course of chemotherapy and their cancer disappears, never to return. In an era when hundreds of thousands of cancer genomes have been sequenced, a remarkable fact persists: in most patients who have been cured, we still do not fully understand the mechanisms underlying the therapeutic index by which the tumour cells are killed, but normal cells are somehow spared. In contrast, in more recent years, patients with cancer have benefited from targeted therapies that usually do not cure but whose mechanisms of therapeutic index are, at least superficially, understood. In this Perspective, we will explore the various and sometimes contradictory models that have attempted to explain why chemotherapy can cure some patients with cancer, and what gaps in our understanding of the therapeutic index of chemotherapy remain to be filled. We will summarize principles which have benefited curative conventional chemotherapy regimens in the past, principles which might be deployed in constructing combinations that include modern targeted therapies. Conventional chemotherapy has successfully cured millions of patients with cancer, yet the mechanisms of action for this remain unclear. In this Perspective, Letai and de The assess the existing mechanisms proposed for the success of chemotherapy, identify gaps in our understanding and suggest principles for improving the utility of conventional chemotherapy to enhance treatment efficacy.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 3","pages":"209-218"},"PeriodicalIF":72.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825499","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

Nanotubes power up T cells 纳米管为T细胞提供能量

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-12-03 DOI: 10.1038/s41568-024-00782-8

Gabrielle Brewer

引用次数: 0

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 72.5 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":"10.1038/s41568-024-00775-7","url":null,"abstract":"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 RB1 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. Genetic predisposition is the major known cause of cancer in children and adolescents. In this Review, Kratz highlights the genetic architecture of cancer in children and adolescents, examining cancer predisposition syndromes, cancer predisposition genes, embryonic mosaicism and polygenic risk scores, focusing on their roles in cancer prediction, prevention, surveillance and therapy.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 2","pages":"109-128"},"PeriodicalIF":72.5,"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

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 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-12-02 DOI: 10.1038/s41568-024-00780-w

Shaon Chakrabarti

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 72.5 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":"10.1038/s41568-024-00772-w","url":null,"abstract":"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. Androgen receptor (AR) signalling plays an important role in several cancers beyond prostate cancer. This Review highlights the context-dependent functions of AR in non-prostatic malignancies, examining the intrinsic function of AR in cancer cells and the tumour microenvironment, and summarizes ongoing AR-targeted clinical trials.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 2","pages":"93-108"},"PeriodicalIF":72.5,"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":"10.1038/s41568-024-00769-5","url":null,"abstract":"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. Chromothripsis is an extreme form of chromosome instability that causes the acquisition of multiple genomic aberrations. Simovic-Lorenz and Ernst discuss mechanistic models of chromothripsis and outline its role in cancer development and tumour evolution. Vulnerabilities of chromothriptic tumours that could be therapeutically exploited are also discussed.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 2","pages":"79-92"},"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 72.5 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

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 72.5 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":"10.1038/s41568-024-00768-6","url":null,"abstract":"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. In this Review, Wang and Zhang summarize the major findings of genetic and epigenetic association studies performed on cohorts of survivors of childhood cancer, which provide insights into the long-term adverse effects related to cancer therapy, and present suggestions for a future survivorship research strategy to inform precision survivorship care.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 2","pages":"129-144"},"PeriodicalIF":72.5,"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

引用次数: 0