Nature Reviews Clinical Oncology最新文献

Opportunities and challenges for MRD assessment in the clinical management of multiple myeloma

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-04-07 DOI: 10.1038/s41571-025-01017-x

Bruno Paiva, Qian Shi, Noemi Puig, Maria-Teresa Cedena, Alberto Orfao, Brian G. M. Durie, Nikhil C. Munshi, Jesús San-Miguel

{"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":"https://doi.org/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.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"73 1","pages":""},"PeriodicalIF":78.8,"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}

引用次数: 0

HER2 testing: evolution and update for a companion diagnostic assay

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-04-07 DOI: 10.1038/s41571-025-01016-y

Charles J. Robbins, Katherine M. Bates, David L. Rimm

{"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":"https://doi.org/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.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"34 1","pages":""},"PeriodicalIF":78.8,"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}

引用次数: 0

Epidemiology, pathogenesis, biology and evolving management of MSI-H/dMMR cancers

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-04-03 DOI: 10.1038/s41571-025-01015-z

Margherita Ambrosini, Paolo Manca, Vincenzo Nasca, Carolina Sciortino, Filippo Ghelardi, Jenny F. Seligmann, Julien Taieb, Filippo Pietrantonio

{"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":"https://doi.org/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.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"37 1","pages":""},"PeriodicalIF":78.8,"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}

引用次数: 0

Surrogate end points in oncology: the speed–uncertainty trade-off from the patients’ perspective

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-03-24 DOI: 10.1038/s41571-025-01007-z

Vinay Prasad

引用次数: 0

Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-03-19 DOI: 10.1038/s41571-025-01013-1

Alireza Mansouri, Ahmad Ozair, Debarati Bhanja, Hannah Wilding, Elad Mashiach, Waqas Haque, Nicholas Mikolajewicz, Leonardo de Macedo Filho, Sean S. Mahase, Mitchell Machtay, Philippe Metellus, Frédéric Dhermain, Jason Sheehan, Douglas Kondziolka, L. Dade Lunsford, Ajay Niranjan, Giuseppe Minniti, Jing Li, Steven N. Kalkanis, Patrick Y. Wen, Rupesh Kotecha, Michael W. McDermott, Chetan Bettegowda, Graeme F. Woodworth, Paul D. Brown, Arjun Sahgal, Manmeet S. Ahluwalia

{"title":"Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care","authors":"Alireza Mansouri, Ahmad Ozair, Debarati Bhanja, Hannah Wilding, Elad Mashiach, Waqas Haque, Nicholas Mikolajewicz, Leonardo de Macedo Filho, Sean S. Mahase, Mitchell Machtay, Philippe Metellus, Frédéric Dhermain, Jason Sheehan, Douglas Kondziolka, L. Dade Lunsford, Ajay Niranjan, Giuseppe Minniti, Jing Li, Steven N. Kalkanis, Patrick Y. Wen, Rupesh Kotecha, Michael W. McDermott, Chetan Bettegowda, Graeme F. Woodworth, Paul D. Brown, Arjun Sahgal, Manmeet S. Ahluwalia","doi":"10.1038/s41571-025-01013-1","DOIUrl":"https://doi.org/10.1038/s41571-025-01013-1","url":null,"abstract":"The management of brain metastases is challenging and should ideally be coordinated through a multidisciplinary approach. Stereotactic radiosurgery (SRS) has been the cornerstone of management for most patients with oligometastatic central nervous system involvement (one to four brain metastases), and several technological and therapeutic advances over the past decade have broadened the indications for SRS to include polymetastatic central nervous system involvement (>4 brain metastases), preoperative application and fractionated SRS, as well as combinatorial approaches with targeted therapy and immune-checkpoint inhibitors. For example, improved imaging and frameless head-immobilization technologies have facilitated fractionated SRS for large brain metastases or postsurgical cavities, or lesions in proximity to organs at risk. However, these opportunities come with new challenges and questions, including the implications of tumour histology as well as the role and sequencing of concurrent systemic treatments. In this Review, we discuss these advances and associated challenges in the context of ongoing clinical trials, with insights from a global group of experts, including recommendations for current clinical practice and future investigations. The updates provided herein are meaningful for all practitioners in clinical oncology.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"70 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660924","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

Emerging importance of HER3 in tumorigenesis and cancer therapy

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-03-14 DOI: 10.1038/s41571-025-01008-y

Joan T. Garrett, Salomon Tendler, Wasim Feroz, Mary Kate Kilroy, Helena Yu

{"title":"Emerging importance of HER3 in tumorigenesis and cancer therapy","authors":"Joan T. Garrett, Salomon Tendler, Wasim Feroz, Mary Kate Kilroy, Helena Yu","doi":"10.1038/s41571-025-01008-y","DOIUrl":"https://doi.org/10.1038/s41571-025-01008-y","url":null,"abstract":"HER3 is a member of the HER/ErbB family of receptor tyrosine kinases, together with EGFR (HER1), HER2 and HER4. Despite having only weak intrinsic kinase activity, HER3 can contribute to oncogenic signalling via ligand-induced heterodimerization with other HER family members. Evidence indicates that HER3 is altered or aberrantly expressed across a variety of tumour types and can be associated with poor clinical outcomes. Whereas anticancer agents targeting EGFR and HER2 have been approved for decades, no drug targeting HER3 had been approved until very recently. Initial targeting of HER3 with monoclonal antibodies as single agents or in combination with other therapeutics produced disappointing clinical results. Subsequently, efforts have been made to target HER3 with novel agents such as antibody–drug conjugates and bispecific antibodies, with promising efficacy observed in several trials encompassing various tumour types. In December 2024, the HER3 × HER2 bispecific antibody zenocutuzumab was granted FDA Accelerated Approval for the treatment of non-small-cell lung cancers or pancreatic cancers harbouring fusions involving NRG1, the gene encoding the high-affinity HER3 ligand neuregulin 1. In this Review, we provide an essential guide to HER3 signalling and oncogenesis, HER3 expression in cancer and its prognostic implications, oncogenic HER3 somatic mutations as well as rare NRG1 fusions that might depend on HER3 signalling, and the roles of HER3 in resistance to cancer therapies. We also highlight efforts to target HER3 with diverse therapeutic strategies and the potential interplay between HER3 and the antitumour immune response.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"49 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627509","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

Utilizing ctDNA to discover mechanisms of resistance to targeted therapies in patients with metastatic NSCLC: towards more informative trials

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-03-14 DOI: 10.1038/s41571-025-01011-3

Sophie M. Ernst, Mihaela Aldea, Jan H. von der Thüsen, Adrianus J. de Langen, Egbert F. Smit, Marthe S. Paats, Joachim G. J. V. Aerts, Laura Mezquita, Sanjay Popat, Benjamin Besse, Jordi Remon, Christian Rolfo, Hendrikus J. Dubbink, Anne-Marie C. Dingemans

{"title":"Utilizing ctDNA to discover mechanisms of resistance to targeted therapies in patients with metastatic NSCLC: towards more informative trials","authors":"Sophie M. Ernst, Mihaela Aldea, Jan H. von der Thüsen, Adrianus J. de Langen, Egbert F. Smit, Marthe S. Paats, Joachim G. J. V. Aerts, Laura Mezquita, Sanjay Popat, Benjamin Besse, Jordi Remon, Christian Rolfo, Hendrikus J. Dubbink, Anne-Marie C. Dingemans","doi":"10.1038/s41571-025-01011-3","DOIUrl":"https://doi.org/10.1038/s41571-025-01011-3","url":null,"abstract":"Advances in targeted therapies for patients with non-small-cell lung cancer have substantially improved the outcomes of those with actionable alterations in certain oncogenic driver genes. However, acquired resistance to these targeted therapies remains a major challenge. Understanding the mechanisms underlying acquired resistance will be crucial for the development of strategies that might either overcome this effect or delay the onset. Circulating tumour DNA, owing to the need for only minimally invasive sampling and a potential role as both a prognostic and predictive biomarker, is increasingly being used in both research and clinical practice. Several studies have explored the landscape of acquired resistance to targeted therapies using this approach. However, the methodologies of the published studies vary widely, and several major challenges remain in addressing the practical difficulties associated with these methods. These challenges currently limit the depth of research insight provided by the available data. In this Perspective, we review clinical reports describing the use of circulating tumour DNA to detect mechanisms of acquired resistance to targeted therapies, predominantly in patients with advanced-stage non-small-cell lung cancer, and highlight key unresolved questions with the aim of moving towards more-informative research studies.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"183 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627420","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

Reduced-volume radiotherapy for locally advanced NPC improves QOL without compromising efficacy

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-03-11 DOI: 10.1038/s41571-025-01014-0

David Killock

引用次数: 0

Hodgkin lymphoma: great progress with room for improvement

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-03-10 DOI: 10.1038/s41571-025-01012-2

Paul J. Bröckelmann

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MORPHEUS-Liver provides a way forward in expanding the immunotherapy options for hepatocellular carcinoma