Nature Reviews Clinical Oncology最新文献

{"title":"CABINET presents cabozantinib as a new treatment option for NETs","authors":"David Killock","doi":"10.1038/s41571-024-00949-0","DOIUrl":"10.1038/s41571-024-00949-0","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"766-766"},"PeriodicalIF":81.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313846","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":"Neoadjuvant immunotherapy for dMMR and pMMR colorectal cancers: therapeutic strategies and putative biomarkers of response","authors":"Christopher J. M. Williams, Allyson M. Peddle, Pashtoon M. Kasi, Jenny F. Seligmann, Campbell S. Roxburgh, Gary W. Middleton, Sabine Tejpar","doi":"10.1038/s41571-024-00943-6","DOIUrl":"10.1038/s41571-024-00943-6","url":null,"abstract":"Approximately 15% of locally advanced colorectal cancers (CRC) have DNA mismatch repair deficiency (dMMR), resulting in high microsatellite instability and a high tumour mutational burden. These cancers are frequently sensitive to therapy with immune-checkpoint inhibitors (ICIs) in the metastatic setting. This sensitivity seems to be even more pronounced in locally advanced disease, and organ preservation has become a realistic aim in ongoing clinical trials involving patients with dMMR rectal cancer. By contrast, metastatic CRCs with proficient DNA mismatch repair (pMMR) are generally resistant to ICIs, although a proportion of locally advanced pMMR tumours seem to have a high degree of sensitivity to ICIs. In this Review, we describe the current and emerging clinical evidence supporting the use of neoadjuvant ICIs in patients with dMMR and pMMR CRC, and the potential advantages (based on a biological rationale) of such an approach. We discuss how neoadjuvant ‘window-of-opportunity’ trials are being leveraged to progress biomarker discovery and we provide an overview of potential predictive biomarkers of response to ICIs, exploring the challenges faced when evaluating such biomarkers in biopsy-derived samples. Lastly, we describe how these discoveries might be used to drive a rational approach to trialling novel immunotherapeutic strategies in patients with pMMR CRC, with the ultimate aim of disease eradication and the generation of long-term immunosurveillance. Locally advanced colorectal cancers (CRCs) with DNA mismatch repair deficiency have sensitivity to immune-checkpoint inhibitors, and evidence suggests that this is also the case for a proportion of proficient DNA mismatch repair CRCs. The authors of this Review describe the emerging clinical evidence supporting the use of neoadjuvant immune-checkpoint inhibitors in patients with CRC and discuss how clinical research (including on biomarkers) can be used to improve clinical outcomes in this setting.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 12","pages":"839-851"},"PeriodicalIF":81.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41571-024-00943-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313847","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}

{"title":"A new standard of care for leiomyosarcoma","authors":"Peter Sidaway","doi":"10.1038/s41571-024-00947-2","DOIUrl":"10.1038/s41571-024-00947-2","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"766-766"},"PeriodicalIF":81.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245344","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":"Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance","authors":"Adrienne G. Waks, Olga Martínez-Sáez, Paolo Tarantino, Fara Braso-Maristany, Tomás Pascual, Javier Cortés, Sara M. Tolaney, Aleix Prat","doi":"10.1038/s41571-024-00939-2","DOIUrl":"10.1038/s41571-024-00939-2","url":null,"abstract":"HER2-targeted therapies for patients with HER2+ breast cancer are rapidly evolving, offering a range of more complex and personalized treatment options. Currently, an array of anti-HER2 monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates are administered, sometimes alongside chemotherapy or endocrine therapy, both in curative and palliative contexts. However, the heterogeneous nature of HER2+ breast cancer demands a deeper understanding of disease biology and its role in responsiveness to novel HER2-targeted agents, as well as non-HER2-targeted therapies, in order to optimize patient outcomes. In this Review, we revisit the mechanisms of action of HER2-targeted agents, examine the evidence supporting the use of dual HER2 blockade in patients with HER2-amplified tumours, and explore the role of biomarkers in guiding future treatment strategies. We also discuss potential implications for the future treatment of patients with HER2+ breast cancer. Patients with HER2+ breast cancer often respond to trastuzumab, although acquired resistance is common and can involve a range of mechanisms. reflecting the highly heterogeneous biology of this breast cancer subtype. In this Review, the authors describe the role of dual HER2 blockade, involving the co-administration of two HER2-targeted therapies (including monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates) in patients with HER2+ breast cancer.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"818-832"},"PeriodicalIF":81.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174961","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":"Vorasidenib: a new hope or a false promise for patients with low-grade glioma?","authors":"Stanislav Lazarev, Kunal K. Sindhu","doi":"10.1038/s41571-024-00944-5","DOIUrl":"10.1038/s41571-024-00944-5","url":null,"abstract":"Despite recent FDA approval, the clinical utility of vorasidenib in the treatment of IDH-mutant low-grade gliomas remains unclear. Herein, we critique the pivotal trial of vorasidenib, and highlight the questionable choice of control intervention and end points, ethical concerns, as well as the uncertain efficacy observed, and argue that the approval might be premature given the high cost of this drug and lack of clear benefit over standard treatments.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 12","pages":"835-836"},"PeriodicalIF":81.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170751","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":"New clinical trials in CUP and a novel paradigm in cancer classification","authors":"Elie Rassy, Fabrice André","doi":"10.1038/s41571-024-00942-7","DOIUrl":"10.1038/s41571-024-00942-7","url":null,"abstract":"Precision oncology has reached a milestone as data from two trials in which molecular profiling guided both site-specific and tumour-agnostic therapies indicate improved survival outcomes in patients with cancer of unknown primary. These findings can also be extrapolated and support the use of tissue-agnostic approaches in general, and also suggest that the tissue of origin might have a role in the agnostic classification of cancers and their response to treatment.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 12","pages":"833-834"},"PeriodicalIF":81.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166194","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 age of foundation models","authors":"Jana Lipkova, Jakob Nikolas Kather","doi":"10.1038/s41571-024-00941-8","DOIUrl":"10.1038/s41571-024-00941-8","url":null,"abstract":"The development of clinically relevant artificial intelligence (AI) models has traditionally required access to extensive labelled datasets, which inevitably centre AI advances around large centres and private corporations. Data availability has also dictated the development of AI applications: most studies focus on common cancer types, and leave rare diseases behind. However, this paradigm is changing with the advent of foundation models, which enable the training of more powerful and robust AI systems using much smaller datasets.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"769-770"},"PeriodicalIF":81.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137934","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":"Immunotherapy for ovarian cancer: towards a tailored immunophenotype-based approach","authors":"Eleonora Ghisoni, Matteo Morotti, Apostolos Sarivalasis, Alizée J. Grimm, Lana Kandalaft, Denarda Dangaj Laniti, George Coukos","doi":"10.1038/s41571-024-00937-4","DOIUrl":"10.1038/s41571-024-00937-4","url":null,"abstract":"Despite documented evidence that ovarian cancer cells express immune-checkpoint molecules, such as PD-1 and PD-L1, and of a positive correlation between the presence of tumour-infiltrating lymphocytes and favourable overall survival outcomes in patients with this tumour type, the results of trials testing immune-checkpoint inhibitors (ICIs) in these patients thus far have been disappointing. The lack of response to ICIs can be attributed to tumour heterogeneity as well as inherent or acquired resistance associated with the tumour microenvironment (TME). Understanding tumour immunobiology, discovering biomarkers for patient selection and establishing optimal treatment combinations remains the hope but also a key challenge for the future application of immunotherapy in ovarian cancer. In this Review, we summarize results from trials testing ICIs in patients with ovarian cancer. We propose the implementation of a systematic CD8+ T cell-based immunophenotypic classification of this malignancy, followed by discussions of the preclinical data providing the basis to treat such immunophenotypes with combination immunotherapies. We posit that the integration of an accurate TME immunophenotype characterization with genetic data can enable the design of tailored therapeutic approaches and improve patient recruitment in clinical trials. Lastly, we propose a roadmap incorporating tissue-based profiling to guide future trials testing adoptive cell therapy approaches and assess novel immunotherapy combinations while promoting collaborative research. Although ovarian cancer is considered an immunoreactive disease, moderate to no efficacy has been shown in the trials testing immune-checkpoint inhibitors in these patients performed thus far. The authors of this Review summarize these results and propose a systematic classification of ovarian cancer based on CD8+ T cell immunophenotypes that, integrated with genetic data, can enable the design of tailored therapeutic approaches, including adoptive cell therapy and novel immunotherapy combinations.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"801-817"},"PeriodicalIF":81.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130683","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":"Redefining priorities: a call for patient-centred cancer care and research","authors":"Carolyn Taylor","doi":"10.1038/s41571-024-00940-9","DOIUrl":"10.1038/s41571-024-00940-9","url":null,"abstract":"My close experience with cancer and interactions with other patients, caregivers and health-care providers have shaped my belief that patients must be at the centre of research and care. In this Comment, I advocate for a redirection of research efforts in order to measure patient-centred outcomes and address health disparities.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"764-765"},"PeriodicalIF":81.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41571-024-00940-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142117994","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}

{"title":"Translating biological insights into improved management of endometrial cancer","authors":"Jeffrey A. How, Amir A. Jazaeri, Shannon N. Westin, Barrett C. Lawson, Ann H. Klopp, Pamela T. Soliman, Karen H. Lu","doi":"10.1038/s41571-024-00934-7","DOIUrl":"10.1038/s41571-024-00934-7","url":null,"abstract":"Endometrial cancer (EC) is the most common gynaecological cancer among women in high-income countries, with both incidence and mortality continuing to increase. The complexity of the management of patients with EC has evolved with greater comprehension of the underlying biology and heterogeneity of this disease. With a growing number of novel therapeutic agents available, emerging treatment regimens seem to have the potential to help to address the concerning trends in EC-related mortality. In this Review, we describe the epidemiology, histopathology and molecular classification of EC as well as the role of the new (2023) International Federation of Gynecologists and Obstetricians (FIGO) staging model. Furthermore, we provide an overview of disease management in the first-line and recurrent disease settings. With increasing use of molecular profiling and updates in treatment paradigms, we also summarize new developments in this rapidly changing treatment landscape. Endometrial cancer is the commonest gynaecological cancer in economically developed countries, and both the incidence and mortality continue to increase. This increasing prevalence highlights the need for novel treatment approaches that will improve patient outcomes. In this Review, the authors describe the epidemiology and standard-of-care treatment approaches for patients with endometrial cancer, as well as highlighting the importance of understanding tumour biology and incorporating this knowledge into better-informed treatment strategies for specific subgroups of patients.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"781-800"},"PeriodicalIF":81.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090060","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}