Pub Date : 2025-11-27DOI: 10.1038/s41571-025-01095-x
Sara Coca Membribes, Bernadett Szabados, Thomas Powles
Molecularly targeted agents and immune checkpoint inhibitors (ICIs) are transforming the treatment landscape for patients with advanced-stage urothelial carcinoma (aUC), although trials testing these novel agents have shown mixed results. In this context, the identification of biomarkers has seen limited success: while activating mutations in FGFR3 are now established as an actionable biomarker to guide treatment with FGFR inhibitors, PD-L1 expression has shown inconsistent value as a predictive biomarker of response to ICIs. The identification of prognostic and predictive biomarkers for ICIs, antibody–drug conjugates and targeted therapies is an active area of research; promising candidates include tumour mutational burden and HER2 overexpression. In the past few years, circulating tumour DNA has emerged as a minimally invasive biomarker, with increasing data supporting its prognostic value and utility for monitoring clinical responses. In this Review, we address these developments and discuss biomarkers that could have clinical utility in patients with aUC. The identification of prognostic and predictive biomarkers for immune checkpoint inhibitors, antibody–drug conjugates and targeted therapies for urothelial carcinoma is currently an active area of research. In this setting, circulating tumour DNA is emerging as a minimally invasive biomarker with utility for monitoring clinical responses. The authors of this Review discuss biomarkers that could have clinical utility in patients with this malignancy
{"title":"Towards biomarker-driven therapies for urothelial carcinoma","authors":"Sara Coca Membribes, Bernadett Szabados, Thomas Powles","doi":"10.1038/s41571-025-01095-x","DOIUrl":"10.1038/s41571-025-01095-x","url":null,"abstract":"Molecularly targeted agents and immune checkpoint inhibitors (ICIs) are transforming the treatment landscape for patients with advanced-stage urothelial carcinoma (aUC), although trials testing these novel agents have shown mixed results. In this context, the identification of biomarkers has seen limited success: while activating mutations in FGFR3 are now established as an actionable biomarker to guide treatment with FGFR inhibitors, PD-L1 expression has shown inconsistent value as a predictive biomarker of response to ICIs. The identification of prognostic and predictive biomarkers for ICIs, antibody–drug conjugates and targeted therapies is an active area of research; promising candidates include tumour mutational burden and HER2 overexpression. In the past few years, circulating tumour DNA has emerged as a minimally invasive biomarker, with increasing data supporting its prognostic value and utility for monitoring clinical responses. In this Review, we address these developments and discuss biomarkers that could have clinical utility in patients with aUC. The identification of prognostic and predictive biomarkers for immune checkpoint inhibitors, antibody–drug conjugates and targeted therapies for urothelial carcinoma is currently an active area of research. In this setting, circulating tumour DNA is emerging as a minimally invasive biomarker with utility for monitoring clinical responses. The authors of this Review discuss biomarkers that could have clinical utility in patients with this malignancy","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 2","pages":"92-106"},"PeriodicalIF":82.2,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609150","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}
Pub Date : 2025-11-25DOI: 10.1038/s41571-025-01108-9
Milit S. Patel, Edward Christopher Dee, Nancy Y. Lee
Artificial intelligence (AI) excels at rapid data synthesis and pattern recognition, yet the practice of oncology demands nuanced clinical judgement, ethical reasoning and authentic empathy — qualities only humans can provide. The future of cancer care lies in synergy: AI augmenting human expertise, not replacing it. Excellence emerges when computational power meets clinical wisdom.
{"title":"AI and human expertise in cancer care — striving for synergy","authors":"Milit S. Patel, Edward Christopher Dee, Nancy Y. Lee","doi":"10.1038/s41571-025-01108-9","DOIUrl":"10.1038/s41571-025-01108-9","url":null,"abstract":"Artificial intelligence (AI) excels at rapid data synthesis and pattern recognition, yet the practice of oncology demands nuanced clinical judgement, ethical reasoning and authentic empathy — qualities only humans can provide. The future of cancer care lies in synergy: AI augmenting human expertise, not replacing it. Excellence emerges when computational power meets clinical wisdom.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 2","pages":"87-88"},"PeriodicalIF":82.2,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593613","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}
Pub Date : 2025-11-20DOI: 10.1038/s41571-025-01105-y
Sacha Gnjatic
A recent Nature article reports that mRNA vaccines against SARS-CoV-2 confer improved survival among patients with advanced-stage non-small-cell lung cancer or melanoma receiving immune-checkpoint inhibitors owing to activation of systemic immunity, potentiating antitumour responses. This retrospective proof-of-principle study indicates the potential for combined therapeutic interventions, although both the timing of vaccination as well as the nature of the elicited immune responses requires further investigation.
{"title":"Could a COVID-19 vaccine improve the effectiveness of cancer immunotherapy?","authors":"Sacha Gnjatic","doi":"10.1038/s41571-025-01105-y","DOIUrl":"10.1038/s41571-025-01105-y","url":null,"abstract":"A recent Nature article reports that mRNA vaccines against SARS-CoV-2 confer improved survival among patients with advanced-stage non-small-cell lung cancer or melanoma receiving immune-checkpoint inhibitors owing to activation of systemic immunity, potentiating antitumour responses. This retrospective proof-of-principle study indicates the potential for combined therapeutic interventions, although both the timing of vaccination as well as the nature of the elicited immune responses requires further investigation.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 2","pages":"90-91"},"PeriodicalIF":82.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145554116","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}
Pub Date : 2025-11-11DOI: 10.1038/s41571-025-01084-0
Dylan P. McClurg, Sally Pan, Rebecca C. Fitzgerald, Christopher M. Jones
Oesophageal adenocarcinoma (OAC) and its precursor condition, Barrett oesophagus, are characterized by phenotypic and molecular intertumoural and intratumoural heterogeneity. This heterogeneity arises in space and time through a complex and still poorly understood interplay between cancer-cell-intrinsic factors, the tumour microenvironment and external influences, such as exposure to anticancer therapies. Together, these elements contribute to a high degree of resistance to therapy while limiting the development of novel targeted therapies and the identification of predictive biomarkers. This situation is exacerbated both in Barrett oesophagus and OAC by a historical clinical reliance on biopsy samples that reflect disease status only at a single location and timepoint. A better understanding of heterogeneity is therefore vital to improve efforts to intercept the development of and optimize treatments for OAC. In this Review, we provide an overview of current and future directions of research on the heterogeneity of Barrett oesophagus and OAC, summarizing our knowledge of the factors that influence heterogeneity, and its consequences across the spectrum of these diseases. A better understanding of the development and progression of heterogeneity in oesophageal adenocarcinoma and its precursor condition, Barrett oesophagus, is crucial for improving surveillance and treatment strategies. The authors of this Review outline the current knowledge of the causes, mediators and therapeutic implications of spatial and temporal heterogeneity in these diseases.
{"title":"The biology and therapeutic implications of heterogeneity in Barrett oesophagus and oesophageal adenocarcinoma","authors":"Dylan P. McClurg, Sally Pan, Rebecca C. Fitzgerald, Christopher M. Jones","doi":"10.1038/s41571-025-01084-0","DOIUrl":"10.1038/s41571-025-01084-0","url":null,"abstract":"Oesophageal adenocarcinoma (OAC) and its precursor condition, Barrett oesophagus, are characterized by phenotypic and molecular intertumoural and intratumoural heterogeneity. This heterogeneity arises in space and time through a complex and still poorly understood interplay between cancer-cell-intrinsic factors, the tumour microenvironment and external influences, such as exposure to anticancer therapies. Together, these elements contribute to a high degree of resistance to therapy while limiting the development of novel targeted therapies and the identification of predictive biomarkers. This situation is exacerbated both in Barrett oesophagus and OAC by a historical clinical reliance on biopsy samples that reflect disease status only at a single location and timepoint. A better understanding of heterogeneity is therefore vital to improve efforts to intercept the development of and optimize treatments for OAC. In this Review, we provide an overview of current and future directions of research on the heterogeneity of Barrett oesophagus and OAC, summarizing our knowledge of the factors that influence heterogeneity, and its consequences across the spectrum of these diseases. A better understanding of the development and progression of heterogeneity in oesophageal adenocarcinoma and its precursor condition, Barrett oesophagus, is crucial for improving surveillance and treatment strategies. The authors of this Review outline the current knowledge of the causes, mediators and therapeutic implications of spatial and temporal heterogeneity in these diseases.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 1","pages":"40-62"},"PeriodicalIF":82.2,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484661","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}
Pub Date : 2025-11-11DOI: 10.1038/s41571-025-01085-z
Jing Zhao, Wanting Xu, Fei Zhou, Xiangyu Zhang, Mo Zhou, Da Miao, Lan Yu, Yongchang Zhang, Junqiang Fan, Caicun Zhou, Wen Li, Tony Mok, Xiuning Le, Molly Li, Yang Xia
Resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a major obstacle in the clinical management of EGFR-mutant non-small-cell lung cancer (NSCLC). Despite the transformative therapeutic activity of the multiple iterations of EGFR TKIs, spanning from first-generation reversible inhibitors such as erlotinib and gefitinib to the current standard-of-care third-generation covalent inhibitor osimertinib, primary or acquired resistance to these agents inevitably emerges via diverse mechanisms. The advent of combination therapies that incorporate chemotherapy, anti-angiogenic agents, bispecific antibodies or antibody–drug conjugates has increased clinical benefit but introduced new resistance phenotypes, underscoring the dynamic plasticity and complexity of tumour evolution under therapeutic pressure. In this Review, we provide a comprehensive synthesis of the molecular mechanisms that underlie resistance to third-generation EGFR TKIs, describe biomarker-guided and biomarker-unselected therapeutic strategies to overcome these mechanisms, and discuss emerging approaches to pre-empt resistance through early application of combination therapies. We highlight the paradigm shift from radiological to molecular monitoring of resistance to therapy and explore how advances in circulating tumour DNA analysis, artificial intelligence and multi-omics might facilitate adaptive treatment strategies. As the therapeutic landscape evolves, a more complete mechanistic understanding of resistance will be essential to guide rational treatment sequencing, inform trial design and improve long-term outcomes for patients with EGFR-mutant NSCLC. Third-generation EGFR tyrosine kinase inhibitors such as osimertinib have substantially improved clinical outcomes in advanced-stage EGFR-mutant non-small-cell lung cancer, but resistance remains inevitable. In this Review, the authors discuss biomarker-directed and biomarker-unselected approaches to overcome established resistance to osimertinib, as well as pre-emptive upfront strategies to delay or prevent the occurrence of osimertinib resistance.
{"title":"Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC — mechanisms and evolving treatment approaches","authors":"Jing Zhao, Wanting Xu, Fei Zhou, Xiangyu Zhang, Mo Zhou, Da Miao, Lan Yu, Yongchang Zhang, Junqiang Fan, Caicun Zhou, Wen Li, Tony Mok, Xiuning Le, Molly Li, Yang Xia","doi":"10.1038/s41571-025-01085-z","DOIUrl":"10.1038/s41571-025-01085-z","url":null,"abstract":"Resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a major obstacle in the clinical management of EGFR-mutant non-small-cell lung cancer (NSCLC). Despite the transformative therapeutic activity of the multiple iterations of EGFR TKIs, spanning from first-generation reversible inhibitors such as erlotinib and gefitinib to the current standard-of-care third-generation covalent inhibitor osimertinib, primary or acquired resistance to these agents inevitably emerges via diverse mechanisms. The advent of combination therapies that incorporate chemotherapy, anti-angiogenic agents, bispecific antibodies or antibody–drug conjugates has increased clinical benefit but introduced new resistance phenotypes, underscoring the dynamic plasticity and complexity of tumour evolution under therapeutic pressure. In this Review, we provide a comprehensive synthesis of the molecular mechanisms that underlie resistance to third-generation EGFR TKIs, describe biomarker-guided and biomarker-unselected therapeutic strategies to overcome these mechanisms, and discuss emerging approaches to pre-empt resistance through early application of combination therapies. We highlight the paradigm shift from radiological to molecular monitoring of resistance to therapy and explore how advances in circulating tumour DNA analysis, artificial intelligence and multi-omics might facilitate adaptive treatment strategies. As the therapeutic landscape evolves, a more complete mechanistic understanding of resistance will be essential to guide rational treatment sequencing, inform trial design and improve long-term outcomes for patients with EGFR-mutant NSCLC. Third-generation EGFR tyrosine kinase inhibitors such as osimertinib have substantially improved clinical outcomes in advanced-stage EGFR-mutant non-small-cell lung cancer, but resistance remains inevitable. In this Review, the authors discuss biomarker-directed and biomarker-unselected approaches to overcome established resistance to osimertinib, as well as pre-emptive upfront strategies to delay or prevent the occurrence of osimertinib resistance.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 1","pages":"63-83"},"PeriodicalIF":82.2,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491614","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}
Pub Date : 2025-11-07DOI: 10.1038/s41571-025-01096-w
Philippe Lambin, Zohaib Salahuddin
{"title":"Reply to ‘Radiomics Quality Score 2.0: what changed from version 1.0 and why it matters’","authors":"Philippe Lambin, Zohaib Salahuddin","doi":"10.1038/s41571-025-01096-w","DOIUrl":"10.1038/s41571-025-01096-w","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 1","pages":"86-86"},"PeriodicalIF":82.2,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455404","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}
Pub Date : 2025-11-07DOI: 10.1038/s41571-025-01098-8
Jeremy McGale, Arnaud Beddok, Lawrence H. Schwartz, Laurent Dercle
{"title":"Radiomics Quality Score 2.0: what changed from version 1.0 and why it matters","authors":"Jeremy McGale, Arnaud Beddok, Lawrence H. Schwartz, Laurent Dercle","doi":"10.1038/s41571-025-01098-8","DOIUrl":"10.1038/s41571-025-01098-8","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 1","pages":"84-85"},"PeriodicalIF":82.2,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455407","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：