Nature Reviews Cancer最新文献

PDX models for functional precision oncology and discovery science 用于功能性精准肿瘤学和发现科学的 PDX 模型

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2024-12-16 DOI: 10.1038/s41568-024-00779-3

Zannel Blanchard, Elisabeth A. Brown, Arevik Ghazaryan, Alana L. Welm

{"title":"PDX models for functional precision oncology and discovery science","authors":"Zannel Blanchard, Elisabeth A. Brown, Arevik Ghazaryan, Alana L. Welm","doi":"10.1038/s41568-024-00779-3","DOIUrl":"https://doi.org/10.1038/s41568-024-00779-3","url":null,"abstract":"Precision oncology relies on detailed molecular analysis of how diverse tumours respond to various therapies, with the aim to optimize treatment outcomes for individual patients. Patient-derived xenograft (PDX) models have been key to preclinical validation of precision oncology approaches, enabling the analysis of each tumour’s unique genomic landscape and testing therapies that are predicted to be effective based on specific mutations, gene expression patterns or signalling abnormalities. To extend these standard precision oncology approaches, the field has strived to complement the otherwise static and often descriptive measurements with functional assays, termed functional precision oncology (FPO). By utilizing diverse PDX and PDX-derived models, FPO has gained traction as an effective preclinical and clinical tool to more precisely recapitulate patient biology using in vivo and ex vivo functional assays. Here, we explore advances and limitations of PDX and PDX-derived models for precision oncology and FPO. We also examine the future of PDX models for precision oncology in the age of artificial intelligence. Integrating these two disciplines could be the key to fast, accurate and cost-effective treatment prediction, revolutionizing oncology and providing patients with cancer with the most effective, personalized treatments.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825466","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

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 78.5 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":"https://doi.org/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.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"22 1","pages":""},"PeriodicalIF":78.5,"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

IF 78.5 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

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":"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.","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

IF 78.5 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

IF 78.5 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 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":"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.","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

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

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":"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.","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