Nature Reviews Clinical Oncology最新文献

{"title":"New standards and new constraints redefine treatment sequencing in platinum-resistant ovarian cancer","authors":"Isabelle Ray-Coquard, Kathleen N. Moore","doi":"10.1038/s41571-026-01168-5","DOIUrl":"10.1038/s41571-026-01168-5","url":null,"abstract":"The therapeutic landscape of platinum-resistant ovarian cancer is rapidly evolving, with recent phase III trials demonstrating, for the first time, meaningful overall survival improvements beyond bevacizumab-based therapy. Herein we discuss how trials such as MIRASOL and, more recently, ENGOT-ov65/KEYNOTE-B96 and GOG30173/ENGOT-ov72/ROSELLA have established new standards of care through distinct biologically driven therapies and outline the new challenges that these approaches expose.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 8","pages":"566-568"},"PeriodicalIF":94.6,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271820","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}

{"title":"Antibody–drug conjugates in gynaecological cancers: opportunities and challenges","authors":"Kathleen N. Moore, Oladapo O. Yeku, Brooke E. Howitt, Hagop Youssoufian, Joyce F. Liu","doi":"10.1038/s41571-026-01164-9","DOIUrl":"10.1038/s41571-026-01164-9","url":null,"abstract":"Antibody–drug conjugates (ADCs) have transformed the cancer therapeutic landscape over the past two decades, profoundly shaping treatment outcomes across a wide array of indications. Three ADCs are currently approved for previously treated gynaecological cancers: mirvetuximab soravtansine for folate receptor-α-positive ovarian cancer, trastuzumab deruxtecan for solid tumours expressing HER2 (defined as a staining intensity on immunohistochemistry of 3+) and tisotumab vedotin for cervical cancer (independent of tissue factor expression). Current research priorities include identifying novel targets, better understanding mechanisms of resistance and sequencing strategies, and optimal management of the toxicities of ADCs. Moreover, rational combinations could reinforce and extend the clinical potential of these agents, as has already been demonstrated with the addition of ADCs to immune checkpoint inhibitors in an effort to amplify antitumour immunity and prolong the durability of clinical responses. In this Review, we provide an overview of the current landscape of ADCs in gynaecological malignancies, highlighting key advances and future opportunities. Three antibody–drug conjugates (ADCs) are currently approved for previously treated gynaecological cancers: mirvetuximab soravtansine for folate receptor-α-positive ovarian cancer, trastuzumab deruxtecan for solid tumours expressing HER2 and tisotumab vedotin for cervical cancer (independent of tissue factor expression). The authors of this Review discuss current priorities in the clinical development of ADCs for gynaecological cancers, such as identifying novel targets, understanding mechanisms of resistance and sequencing strategies, and managing toxicities, highlighting key advances and future opportunities.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 9","pages":"672-693"},"PeriodicalIF":94.6,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271854","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}

{"title":"Teclistamab monotherapy improves survival in RRMM","authors":"Diana Romero","doi":"10.1038/s41571-026-01178-3","DOIUrl":"10.1038/s41571-026-01178-3","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 9","pages":"655-655"},"PeriodicalIF":94.6,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258910","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}

{"title":"Daraxonrasib effective in metastatic pancreatic ductal adenocarcinoma","authors":"Peter Sidaway","doi":"10.1038/s41571-026-01176-5","DOIUrl":"10.1038/s41571-026-01176-5","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 9","pages":"654-654"},"PeriodicalIF":94.6,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239743","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}

{"title":"Potential new standard of care for resectable gastro-oesophageal adenocarcinoma in Asia","authors":"David Killock","doi":"10.1038/s41571-026-01177-4","DOIUrl":"10.1038/s41571-026-01177-4","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 9","pages":"654-654"},"PeriodicalIF":94.6,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239751","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}

{"title":"Adjuvant selpercatinib shows benefit in patients with NSCLC","authors":"Diana Romero","doi":"10.1038/s41571-026-01172-9","DOIUrl":"10.1038/s41571-026-01172-9","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 8","pages":"564-564"},"PeriodicalIF":94.6,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148227166","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}

{"title":"Ivonescimab improves overall survival","authors":"Peter Sidaway","doi":"10.1038/s41571-026-01175-6","DOIUrl":"10.1038/s41571-026-01175-6","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 8","pages":"564-564"},"PeriodicalIF":94.6,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148227119","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}

{"title":"From ASCO 2026","authors":"David Killock","doi":"10.1038/s41571-026-01173-8","DOIUrl":"10.1038/s41571-026-01173-8","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 8","pages":"565-565"},"PeriodicalIF":94.6,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148227089","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}

{"title":"The future is not always uniform: rethinking radiotherapy through spatial fractionation","authors":"Federico Iori, Slavisa Tubin, Waleed F. Mourad, Marco Durante, Yolanda Prezado, Pedro C. Lara, Andrea Botti, Xiaodong Wu, Matthias Guckenberger, on behalf of the ESTRO Focus Group","doi":"10.1038/s41571-026-01161-y","DOIUrl":"10.1038/s41571-026-01161-y","url":null,"abstract":"Radiotherapy has traditionally been guided by the principle that uniform delivery of a tumoricidal dose across the entire target volume maximizes local control. However, this paradigm becomes increasingly constrained in the setting of large, bulky or anatomically complex tumours, in which non-malignant tissue tolerances often preclude homogeneous dose escalation. Spatially fractionated radiotherapy (SFRT) has emerged as a complementary approach that introduces intentional intratumoural dose heterogeneity as an alternative therapeutic strategy when uniform irradiation is not feasible. SFRT involves the delivery of radiation as high-dose ‘peaks’ interspersed with lower-dose ‘valleys’, creating spatial domains that combine focal tumoricidal exposures with partial preservation of vascular, stromal and immune-related functions within the tumour microenvironment. Preclinical investigations and early clinical studies suggest that such architectures might be associated with rapid volumetric tumour regression, acceptable toxicity profiles and modulation of the tumour immune microenvironment, although the underlying mechanisms, generalizability and durability of these effects remain incompletely defined. In this Review, we summarize the conceptual foundations, biological hypotheses and clinical activity of SFRT, spanning macroscopic approaches such as GRID and lattice radiotherapy, biology-guided strategies and submillimetric implementations using minibeams and microbeams. We also highlight key translational and methodological limitations and discuss various challenges relating to dosimetry, biologically meaningful response assessments, patient selection and multicentre reproducibility. Traditional radiotherapy approaches involve the delivery of a uniform radiation dose to the entire tumour. Despite considerable effectiveness, this approach comes with the limitations of a lack of activity against larger tumour volumes as well as off-target irradiation of surrounding non-malignant tissues. Spatially fractionated radiotherapy, involving deliberate non-uniform irradiation, has the potential to address these challenges, with early data suggesting safety and activity in patients with advanced-stage cancers. In this Review, the authors describe the emerging role of spatially fractionated radiotherapy in the management of patients with cancer.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 9","pages":"656-671"},"PeriodicalIF":94.6,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218791","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}

{"title":"Trial design and end points in hepatocellular carcinoma: an EASL–AASLD–ILCA consensus statement","authors":"Josep M. Llovet, Ezequiel Mauro, Lorenza Rimassa, Vincenzo Mazzaferro, Matthias Pinter, Robin Kate Kelley, Stephen L. Chan, Laura Kulik, Anjana Pillai, Lewis Roberts, Bruno Sangro, Teresa Casanovas, David E. Kaplan, Arndt Vogel, Mark Yarchoan, Richard S. Finn, Tim Meyer, Amit G. Singal","doi":"10.1038/s41571-026-01160-z","DOIUrl":"10.1038/s41571-026-01160-z","url":null,"abstract":"The management of hepatocellular carcinoma (HCC) has undergone radical change over the past decade. Immunotherapies now dominate the treatment of advanced-stage disease and are increasingly being evaluated in perioperative and intermediate-stage settings. However, in some instances, positive phase III trials have not translated into adoption by guidelines or regulatory agencies, highlighting the need to harmonize and update the current standards for trial design and end points. In response to these challenges, four scientific societies — the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), the International Liver Cancer Association (ILCA) and the American Society of Clinical Oncology (ASCO) — appointed representatives to develop a consensus recommendations document addressing current unmet needs and future challenges in HCC trial design and end points. Through a modified Delphi process, 102 consensus statements were developed across several distinct domains: surveillance; early-stage, intermediate-stage and advanced-stage disease; transplant-related contexts; regulatory considerations; and emerging topics. The document rigorously defines target populations, stratification factors, control arms and benchmarks for expected clinical benefit. Collectively, this consensus is intended to provide a dynamic, evidence-based, multisociety roadmap for optimizing trial design, accelerating therapeutic development and improving clinically meaningful outcomes in patients with HCC. Despite considerable improvements in the outcomes in patients with hepatocellular carcinoma (HCC), many outstanding research questions remain unanswered. Furthermore, significant findings from successful phase III trials have not always been translated into guideline-recommended therapies, implying a need for improved standardization of trial end points. In this Consensus Statement, representatives of four major societies (the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), the International Liver Cancer Association (ILCA) and the American Society of Clinical Oncology (ASCO)) convened to provide guidance on end point selection for clinical trials conducted in various settings including surveillance, and early-stage, intermediate-stage and advanced-stage HCC.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 8","pages":"619-647"},"PeriodicalIF":94.6,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41571-026-01160-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218766","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}