Nature Reviews Clinical Oncology最新文献

{"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}

{"title":"Tumour mutational burden: clinical utility, challenges and emerging improvements","authors":"Jan Budczies, Daniel Kazdal, Michael Menzel, Susanne Beck, Klaus Kluck, Christian Altbürger, Constantin Schwab, Michael Allgäuer, Aysel Ahadova, Matthias Kloor, Peter Schirmacher, Solange Peters, Alwin Krämer, Petros Christopoulos, Albrecht Stenzinger","doi":"10.1038/s41571-024-00932-9","DOIUrl":"10.1038/s41571-024-00932-9","url":null,"abstract":"Tumour mutational burden (TMB), defined as the total number of somatic non-synonymous mutations present within the cancer genome, varies across and within cancer types. A first wave of retrospective and prospective research identified TMB as a predictive biomarker of response to immune-checkpoint inhibitors and culminated in the disease-agnostic approval of pembrolizumab for patients with TMB-high tumours based on data from the Keynote-158 trial. Although the applicability of outcomes from this trial to all cancer types and the optimal thresholds for TMB are yet to be ascertained, research into TMB is advancing along three principal avenues: enhancement of TMB assessments through rigorous quality control measures within the laboratory process, including the mitigation of confounding factors such as limited panel scope and low tumour purity; refinement of the traditional TMB framework through the incorporation of innovative concepts such as clonal, persistent or HLA-corrected TMB, tumour neoantigen load and mutational signatures; and integration of TMB with established and emerging biomarkers such as PD-L1 expression, microsatellite instability, immune gene expression profiles and the tumour immune contexture. Given its pivotal functions in both the pathogenesis of cancer and the ability of the immune system to recognize tumours, a profound comprehension of the foundational principles and the continued evolution of TMB are of paramount relevance for the field of oncology. Tumour mutational burden (TMB), reflecting the number of mutations present in the DNA of a tumour, is a biologically appealing biomarker of a response to immune-checkpoint inhibitors (ICIs). Nonetheless, the clinical predictive value of TMB for ICI response has thus far been mixed, with robust associations seen only for a few ICI-responsive cancer types. In this Review, the authors summarize the available data on TMB and discuss ongoing research efforts to improve the clinical utility of this biomarker.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 10","pages":"725-742"},"PeriodicalIF":81.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41571-024-00932-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081117","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":"Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer","authors":"Maxwell R. Lloyd, Komal Jhaveri, Kevin Kalinsky, Aditya Bardia, Seth A. Wander","doi":"10.1038/s41571-024-00935-6","DOIUrl":"10.1038/s41571-024-00935-6","url":null,"abstract":"Anti-oestrogen-based therapies, often combined with a CDK4/6 inhibitor, are the current standard-of-care first-line therapy for patients with advanced-stage hormone receptor-positive (HR+) breast cancer. Resistance to anti-oestrogen agents inevitably occurs, mediated by oestrogen receptor (ER)-dependent or ER-independent mechanisms that drive tumour progression. Emerging endocrine therapies include, but are not limited to, next-generation oral ER degraders and proteolysis targeting chimeras, which might be particularly effective in patients with ESR1-mutant breast cancer. Furthermore, cancers harbouring driver alterations in oncogenic signalling pathways, including AKT and PI3K, might be susceptible to novel combination strategies involving targeted inhibitors. Next-generation CDK2/4 inhibitors are an area of active clinical investigation, and efforts are ongoing to evaluate the role of sequential CDK inhibition. Approved and emerging antibody–drug conjugates exploiting novel target antigens have also demonstrated promising clinical activity. These novel agents, as well as further identification and characterization of predictive biomarkers, will hopefully continue to improve clinical outcomes, reduce the incidence of toxicities, and limit the extent of overtreatment in this population. In this Review, we describe the evolving treatment paradigm for patients with metastatic HR+ breast cancer in light of the growing armamentarium of drugs and biomarkers that will help to shape the future therapeutic landscape. These strategies are expected to involve tumour molecular profiling to enable the delivery of precision medicine. Patients with advanced-stage hormone receptor-positive (HR+) breast cancer typically receive first-line treatment with anti-oestrogen-based agents, often combined with a CDK4/6 inhibitor, although resistance remains common. The authors of this Review discuss how a variety of novel endocrine therapies together with tumour molecular profiling could shape the future therapeutic landscape for these patients.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 10","pages":"743-761"},"PeriodicalIF":81.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042410","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 MARIPOSA trials — implications for the treatment of EGFR-mutant NSCLC","authors":"Fatemeh Ardeshir-Larijani, Suresh S. Ramalingam","doi":"10.1038/s41571-024-00938-3","DOIUrl":"10.1038/s41571-024-00938-3","url":null,"abstract":"In the past 2 years, substantial improvements have been made in the management of advanced-stage EGFR-mutant non-small-cell lung cancer. Recent studies have suggested added benefit from the combination of third-generation tyrosine-kinase inhibitors with either chemotherapy or a bispecific antibody targeting EGFR and MET. Herein, we summarize these advances and their implications for clinical practice.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 11","pages":"767-768"},"PeriodicalIF":81.1,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002772","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":"Applications of cell therapy in the treatment of virus-associated cancers","authors":"Keri Toner, Chase D. McCann, Catherine M. Bollard","doi":"10.1038/s41571-024-00930-x","DOIUrl":"10.1038/s41571-024-00930-x","url":null,"abstract":"A diverse range of viruses have well-established roles as the primary driver of oncogenesis in various haematological malignancies and solid tumours. Indeed, estimates suggest that approximately 1.5 million patients annually are diagnosed with virus-related cancers. The predominant human oncoviruses include Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis B and C viruses (HBV and HCV), human papillomavirus (HPV), human T-lymphotropic virus type 1 (HTLV1), and Merkel cell polyomavirus (MCPyV). In addition, although not inherently oncogenic, human immunodeficiency virus (HIV) is associated with immunosuppression that contributes to the development of AIDS-defining cancers (specifically, Kaposi sarcoma, aggressive B cell non-Hodgkin lymphoma and cervical cancer). Given that an adaptive T cell-mediated immune response is crucial for the control of viral infections, increasing research is being focused on evaluating virus-specific T cell therapies for the treatment of virus-associated cancers. In this Review, we briefly outline the roles of viruses in the pathogenesis of these malignancies before describing progress to date in the field of virus-specific T cell therapy and evaluating the potential utility of these therapies to treat or possibly even prevent virus-related malignancies. Several different viruses have a role in cancer pathogenesis, contributing to the development of various haematological malignancies and solid tumours via diverse, multifaceted mechanisms. However, this viral aetiology presents a unique opportunity for adoptive virus-specific T cell (VST) therapy. This Review summarizes the mechanisms of viral carcinogenesis and describes the current clinical experience with adoptive cellular immunotherapies for virus-related cancers, predominantly using non-genetically modified VSTs. The authors also discuss challenges and future directions for the ongoing clinical development of VST therapies.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 10","pages":"709-724"},"PeriodicalIF":81.1,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002770","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}