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Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance 双重 HER2 抑制：协同作用机制、患者选择和耐药性
IF 78.8 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-09-13 DOI: 10.1038/s41571-024-00939-2
Adrienne G. Waks, Olga Martínez-Sáez, Paolo Tarantino, Fara Braso-Maristany, Tomás Pascual, Javier Cortés, Sara M. Tolaney, Aleix Prat
{"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":"https://doi.org/10.1038/s41571-024-00939-2","url":null,"abstract":"<p>HER2-targeted therapies for patients with HER2<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> breast cancer.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":78.8,"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}
引用次数: 0
Vorasidenib: a new hope or a false promise for patients with low-grade glioma? Vorasidenib：低级别胶质瘤患者的新希望还是虚假承诺？
IF 78.8 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-09-12 DOI: 10.1038/s41571-024-00944-5
Stanislav Lazarev, Kunal K. Sindhu
{"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":"https://doi.org/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&nbsp;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":null,"pages":null},"PeriodicalIF":78.8,"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}
引用次数: 0
New clinical trials in CUP and a novel paradigm in cancer classification CUP 的新临床试验和癌症分类的新范例
IF 78.8 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-09-11 DOI: 10.1038/s41571-024-00942-7
Elie Rassy, Fabrice André
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":78.8,"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}
引用次数: 0
The age of foundation models 基础模型时代
IF 78.8 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-09-05 DOI: 10.1038/s41571-024-00941-8
Jana Lipkova, Jakob Nikolas Kather
{"title":"The age of foundation models","authors":"Jana Lipkova, Jakob Nikolas Kather","doi":"10.1038/s41571-024-00941-8","DOIUrl":"https://doi.org/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":null,"pages":null},"PeriodicalIF":78.8,"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}
引用次数: 0
Immunotherapy for ovarian cancer: towards a tailored immunophenotype-based approach 卵巢癌免疫疗法：迈向基于免疫表型的定制方法
IF 78.8 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-09-04 DOI: 10.1038/s41571-024-00937-4
Eleonora Ghisoni, Matteo Morotti, Apostolos Sarivalasis, Alizée J. Grimm, Lana Kandalaft, Denarda Dangaj Laniti, George Coukos
{"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":"https://doi.org/10.1038/s41571-024-00937-4","url":null,"abstract":"<p>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<sup>+</sup> 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.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":78.8,"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}
引用次数: 0
Redefining priorities: a call for patient-centred cancer care and research 重新确定优先事项：呼吁开展以患者为中心的癌症护理和研究
IF 78.8 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-08-29 DOI: 10.1038/s41571-024-00940-9
Carolyn Taylor
{"title":"Redefining priorities: a call for patient-centred cancer care and research","authors":"Carolyn Taylor","doi":"10.1038/s41571-024-00940-9","DOIUrl":"https://doi.org/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":null,"pages":null},"PeriodicalIF":78.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Translating biological insights into improved management of endometrial cancer 将生物学知识转化为更好的子宫内膜癌治疗方法
IF 78.8 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-08-28 DOI: 10.1038/s41571-024-00934-7
Jeffrey A. How, Amir A. Jazaeri, Shannon N. Westin, Barrett C. Lawson, Ann H. Klopp, Pamela T. Soliman, Karen H. Lu
{"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":"https://doi.org/10.1038/s41571-024-00934-7","url":null,"abstract":"<p>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.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":78.8,"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}
引用次数: 0
Tumour mutational burden: clinical utility, challenges and emerging improvements. 肿瘤突变负荷：临床实用性、挑战和新的改进。
IF 81.1 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-08-27 DOI: 10.1038/s41571-024-00932-9
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
{"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":"https://doi.org/10.1038/s41571-024-00932-9","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":81.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer 针对 HR 阳性转移性乳腺癌的精准疗法和新策略
IF 78.8 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-08-23 DOI: 10.1038/s41571-024-00935-6
Maxwell R. Lloyd, Komal Jhaveri, Kevin Kalinsky, Aditya Bardia, Seth A. Wander
{"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":"https://doi.org/10.1038/s41571-024-00935-6","url":null,"abstract":"<p>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<sup>+</sup>) 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 <i>ESR1</i>-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<sup>+</sup> 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.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":78.8,"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}
引用次数: 0
The MARIPOSA trials — implications for the treatment of EGFR-mutant NSCLC MARIPOSA 试验--对治疗表皮生长因子受体突变型 NSCLC 的影响
IF 78.8 1区 医学
Nature Reviews Clinical Oncology Pub Date : 2024-08-19 DOI: 10.1038/s41571-024-00938-3
Fatemeh Ardeshir-Larijani, Suresh S. Ramalingam
{"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":"https://doi.org/10.1038/s41571-024-00938-3","url":null,"abstract":"In the past 2&nbsp;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":null,"pages":null},"PeriodicalIF":78.8,"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}
引用次数: 0
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