Nature Reviews Clinical Oncology最新文献

{"title":"Extended neoadjuvant dostarlimab provides durable benefit in resectable dMMR solid tumours","authors":"Peter Sidaway","doi":"10.1038/s41571-025-01027-9","DOIUrl":"10.1038/s41571-025-01027-9","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 6","pages":"382-382"},"PeriodicalIF":82.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915490","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":"Improving outcomes of patients with pancreatic cancer","authors":"Stephan B. Dreyer, Philip Beer, Sunil R. Hingorani, Andrew V. Biankin","doi":"10.1038/s41571-025-01019-9","DOIUrl":"10.1038/s41571-025-01019-9","url":null,"abstract":"Research studies aimed at improving the outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) have brought about limited progress, and in clinical practice, the optimized use of surgery, chemotherapy and supportive care have led to modest improvements in survival that have probably reached a plateau. As a result, PDAC is expected to be the second leading cause of cancer-related death in Western societies within a decade. The development of therapeutic advances in PDAC has been challenging owing to a lack of actionable molecular targets, a typically immunosuppressive microenvironment, and a disease course characterized by rapid progression and clinical deterioration. Yet, the progress in our understanding of PDAC and identification of novel therapeutic opportunities over the past few years is leading to a strong sense of optimism in the field. In this Perspective, we address the aforementioned challenges, including biological aspects of PDAC that make this malignancy particularly difficult to treat. We explore specific areas with potential for therapeutic advances, including targeting mutant KRAS, novel strategies to harness the antitumour immune response and approaches to early detection, and propose mechanisms to improve clinical trial design and to overcome various community and institutional barriers to progress. The incidence of pancreatic ductal adenocarcinoma (PDAC) has been increasing over the past few decades and survival rates for patients with this malignancy remain dismal. The authors of this Perspective discuss the challenges that have limited progress in the development of treatments for patients with PDAC and present novel approaches that could be leveraged to improve their outcomes.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 6","pages":"439-456"},"PeriodicalIF":82.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914984","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 evolving immuno-angiogenic paradigm in NSCLC: lessons from ivonescimab","authors":"Roy S. Herbst, Lieping Chen","doi":"10.1038/s41571-025-01024-y","DOIUrl":"10.1038/s41571-025-01024-y","url":null,"abstract":"The HARMONi-2 trial demonstrated a significant improvement in progression-free survival with ivonescimab, a bispecific PD-1×VEGF antibody, versus pembrolizumab in patients with PD-L1-positive advanced-stage non-small-cell lung cancer. Ivonescimab might enhance antitumour immunity by normalizing the tumour vasculature and reversing immunosuppression. Although promising, global applicability of ivonescimab awaits further validation, including overall survival results, in diverse populations.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 7","pages":"461-462"},"PeriodicalIF":82.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909866","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":"Durable responses to belzutifan in patients with VHL disease","authors":"Peter Sidaway","doi":"10.1038/s41571-025-01023-z","DOIUrl":"10.1038/s41571-025-01023-z","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 6","pages":"382-382"},"PeriodicalIF":82.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872120","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":"Sacituzumab tirumotecan improves OS in mTNBC","authors":"David Killock","doi":"10.1038/s41571-025-01022-0","DOIUrl":"10.1038/s41571-025-01022-0","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 6","pages":"382-382"},"PeriodicalIF":82.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862185","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":"FDA approvals in 2024: new options for patients across cancer types and therapeutic classes","authors":"Sundeep Agrawal, Esther Park, Paul G. Kluetz","doi":"10.1038/s41571-025-01018-w","DOIUrl":"10.1038/s41571-025-01018-w","url":null,"abstract":"In 2024, the US FDA approved several new agents for the treatment of patients with cancer, including small-molecule inhibitors, immune-checkpoint inhibitors, bispecific antibodies, antibody–drug conjugates and cell and gene therapy products. Areas of regulatory focus included the accelerated approval programme and diligent completion of post-marketing trials, convening of Oncologic Drugs Advisory Committee meetings to ensure transparent discussions of complex regulatory issues, and continuation of robust, meaningful engagement with the oncology community to foster efficient drug development.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 7","pages":"457-458"},"PeriodicalIF":82.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819264","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":"Opportunities and challenges for MRD assessment in the clinical management of multiple myeloma","authors":"Bruno Paiva, Qian Shi, Noemi Puig, Maria-Teresa Cedena, Alberto Orfao, Brian G. M. Durie, Nikhil C. Munshi, Jesús San-Miguel","doi":"10.1038/s41571-025-01017-x","DOIUrl":"10.1038/s41571-025-01017-x","url":null,"abstract":"Measurable residual disease (MRD) assessment is, from the methodological point of view, ready for prime time in multiple myeloma (MM). Abundant evidence underscores the value of MRD status determined using highly sensitive next-generation flow cytometry and next-generation sequencing tests in evaluating response to treatment and, therefore, prognosis in patients with this disease. MRD response assessment and monitoring might present a range of opportunities for individualized patient management. Moreover, the considerable amounts of high-quality and standardized MRD data generated in clinical trials have led to the acceptance of MRD negativity as an early end point for accelerated regulatory approval of treatments for MM. The data leave no doubt that the efficacy of new regimens in inducing deeper and durable MRD-negative responses is connected with prolonged survival. Yet, several evidential, technical and practical challenges continue to limit the implementation of MRD-guided treatment strategies in routine practice, and the use of MRD as a surrogate end point remains controversial to some. In this Review, we draw on past and present research to propose opportunities for overcoming some of these challenges, and to accelerate the use of MRD assessment for improved clinical management of patients with MM. Multiple myeloma is a malignancy at the forefront of measurable residual disease (MRD) assessment. In this Review, the authors describe the evolution of MRD analysis in multiple myeloma from technical and clinical standpoints, and discuss opportunities and challenges for MRD-guided management of this disease.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 6","pages":"424-438"},"PeriodicalIF":82.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789808","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":"HER2 testing: evolution and update for a companion diagnostic assay","authors":"Charles J. Robbins, Katherine M. Bates, David L. Rimm","doi":"10.1038/s41571-025-01016-y","DOIUrl":"10.1038/s41571-025-01016-y","url":null,"abstract":"Human epidermal growth factor receptor 2 (HER2; encoded by ERBB2) testing has been a cornerstone of patient selection for HER2-targeted therapies, principally in breast cancer but also in several other solid tumours. Since the introduction of HercepTest as the original companion diagnostic for trastuzumab, HER2 assessment methods have evolved substantially, incorporating various testing modalities, from western blots, immunohistochemistry and fluorescence in situ hybridization, to early chromogenic quantitative methods and, probably in the future, fully quantitative methods. The advent of highly effective HER2-targeted antibody–drug conjugates with clinical activity at low levels of HER2 expression, such as trastuzumab deruxtecan, has necessitated the re-evaluation of HER2 testing, particularly for HER2-low tumours. In this Review, we provide an in-depth overview of the evolution of HER2 testing, the current clinical guidelines for HER2 testing across various solid tumours, challenges associated with current testing methodologies and the emerging potential of quantitative techniques. We discuss the importance of accurately defining HER2-low expression for therapeutic decision-making and how newer diagnostic approaches, such as quantitative immunofluorescence and RNA-based assays, might address the limitations of traditional immunohistochemistry-based methods. As the use of HER2-targeted therapies continues to expand to a wider range of tumour types, ensuring the precision and accuracy of HER2 testing will be crucial for guiding treatment strategies and improving patient outcomes. The development of companion diagnostic assays enabling the detection and quantification of HER2 expression and ERBB2 amplifications has provided an important early example that has informed the development of many companion diagnostics for the identification of other drug targets. However, the introduction of trastuzumab deruxtecan and, potentially, other novel antibody–drug conjugates has created the need for assays that are much more sensitive. In this Review, the authors describe the historical development of HER2 companion diagnostic assays in breast and other HER2-positive cancers and highlight the possible, future, more sensitive methods of HER2 detection and quantification that might provide the next generation of companion diagnostics.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 6","pages":"408-423"},"PeriodicalIF":82.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797879","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":"Epidemiology, pathogenesis, biology and evolving management of MSI-H/dMMR cancers","authors":"Margherita Ambrosini, Paolo Manca, Vincenzo Nasca, Carolina Sciortino, Filippo Ghelardi, Jenny F. Seligmann, Julien Taieb, Filippo Pietrantonio","doi":"10.1038/s41571-025-01015-z","DOIUrl":"10.1038/s41571-025-01015-z","url":null,"abstract":"Deficiency in DNA mismatch repair (dMMR) is a common pathway of carcinogenesis across different tumour types and confers a characteristic microsatellite instability-high (MSI-H) molecular phenotype. The prevalence of the MSI-H/dMMR phenotype is highest in endometrial and colorectal cancers, and this phenotype is associated with a distinct tumour biology, prognosis and responsiveness to various anticancer treatments. In a minority of patients, MSI-H/dMMR cancers result from an inherited pathogenic variant in the context of Lynch syndrome, which has important implications for familial genetic screening. Whether these hereditary cancers have a different biology and clinical behaviour to their sporadic counterparts remains uncertain. Interest in this tumour molecular subtype has increased following the discovery of the high sensitivity of metastatic MSI-H/dMMR cancers to immune-checkpoint inhibitors (ICIs) in a histology-agnostic manner, which reflects the genomic hypermutation resulting from dMMR that renders these tumours highly immunogenic and immune infiltrated. This vulnerability is now also being exploited in early stage disease settings. Despite this common biological foundation, different MSI-H/dMMR cancers have histotype-specific features that correspond to their particular cell or tissue of origin, which might be associated with differences in prognosis and sensitivity to ICIs. In this Review, we provide an overview of the epidemiology, biology, pathogenesis, clinical diagnosis and treatment of MSI-H/dMMR tumours as a histology-agnostic cancer phenomenon. We also highlight peculiarities associated with specific pathogenetic alterations and histologies of MSI-H/dMMR tumours. Tumours with deficient DNA mismatch repair (dMMR) leading to a microsatellite instability-high (MSI-H) phenotype are characterized by a high burden of immunogenic mutations and, thus, an immunological ‘hot’ microenvironment that is associated with high sensitivity to immune-checkpoint inhibitors. In this Review, the authors discuss the epidemiology, biology, pathogenesis, clinical diagnosis and treatment of MSI-H/dMMR tumours, highlighting idiosyncrasies associated with specific pathogenetic alterations and tumour histologies.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 6","pages":"385-407"},"PeriodicalIF":82.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775600","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":"Surrogate end points in oncology: the speed–uncertainty trade-off from the patients’ perspective","authors":"Vinay Prasad","doi":"10.1038/s41571-025-01007-z","DOIUrl":"10.1038/s41571-025-01007-z","url":null,"abstract":"Surrogate end points in drug regulation are thought to reduce the time required to bring new drugs to market; however, only a few of the drugs approved on the basis of these outcomes have subsequently demonstrated robust improvements in overall survival (OS). If the FDA and other regulators were to shift their priority to patient-centred outcomes, such as OS, I argue that such a shift would probably lead to fewer, but also a higher standard of drugs entering the market, potentially with faster approval decisions because novel therapies would initially be tested in later lines and in patients with a worse prognosis.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 5","pages":"313-314"},"PeriodicalIF":82.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677645","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}