Nature Reviews Clinical Oncology最新文献

{"title":"Minimal residual disease as a target for liquid biopsy in patients with solid tumours","authors":"Klaus Pantel, Catherine Alix-Panabières","doi":"10.1038/s41571-024-00967-y","DOIUrl":"10.1038/s41571-024-00967-y","url":null,"abstract":"Metastasis is the leading cause of cancer-related death in patients with solid tumours. Current imaging technologies are not sufficiently sensitive to detect minimal residual disease (MRD; also known as measurable or molecular residual disease) after initial surgery or chemotherapy, pointing to the need for more sensitive tests to detect remaining traces of cancer in the body. Liquid biopsy, or the analysis of tumour-derived or tumour-induced cells or cellular products in the blood or other body fluids, has opened a new diagnostic avenue to detect and monitor MRD. Liquid biopsy is already used in clinical decision making for patients with haematological malignancies. Here, we review current knowledge on the use of circulating tumour DNA (ctDNA) to detect and monitor MRD in patients with solid tumours. We also discuss how ctDNA-guided MRD detection and characterization could herald a new era of novel ‘post-adjuvant therapies’ with the potential to eliminate MRD and cure patients before terminal metastatic disease is evident on imaging. Liquid biopsy, or the analysis of tumour-derived or tumour-induced cells or cellular products in the blood or other body fluids, is a promising approach to assess minimal residual disease (MRD; also known as measurable or molecular residual disease). The authors of this Review discuss the available evidence on the use of circulating tumour DNA to detect and monitor MRD in patients with solid tumours to enable treatment decisions before terminal metastatic disease is evident on imaging.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 1","pages":"65-77"},"PeriodicalIF":81.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735723","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":"An early switch in first-line therapy improves outcomes of advanced-stage G/GEJC","authors":"David Killock","doi":"10.1038/s41571-024-00974-z","DOIUrl":"10.1038/s41571-024-00974-z","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 1","pages":"1-1"},"PeriodicalIF":81.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712520","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":"HIPEC is effective in patients undergoing cytoreduction for recurrent ovarian cancer","authors":"Peter Sidaway","doi":"10.1038/s41571-024-00973-0","DOIUrl":"10.1038/s41571-024-00973-0","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 1","pages":"2-2"},"PeriodicalIF":81.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712522","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":"Late-line options for patients with metastatic colorectal cancer: a review and evidence-based algorithm","authors":"Paolo Ciracì, Vittorio Studiale, Ada Taravella, Carlotta Antoniotti, Chiara Cremolini","doi":"10.1038/s41571-024-00965-0","DOIUrl":"10.1038/s41571-024-00965-0","url":null,"abstract":"Over the past few years, several novel systemic treatments have emerged for patients with treatment-refractory metastatic colorectal cancer, thus making selection of the most effective later-line therapy a challenge for medical oncologists. Over the past decade, regorafenib and trifluridine–tipiracil were the only available drugs and often provided limited clinical benefit compared to best supportive care. Results from subsequent practice-changing trials opened several novel therapeutic avenues, both for unselected patients (such as trifluridine–tipiracil plus bevacizumab or fruquintinib) and for subgroups defined by the presence of actionable alterations in their tumours (such as HER2-targeted therapies or KRASG12C inhibitors) or with no acquired mechanisms of resistance to the previously received targeted agents in circulating tumour DNA (such as retreatment with anti-EGFR antibodies). In this Review, we provide a comprehensive overview of advances in the field over the past few years and offer a practical perspective on translation of the most relevant results into the daily management of patients with metastatic colorectal cancer using an evidence-based algorithm. Finally, we discuss some of the most appealing ongoing areas of research and highlight approaches with the potential to further expand the therapeutic armamentarium. Over the past few years, several novel therapies, including targeted therapies for specific subgroups as well as several non-targeted therapies, have been developed and approved for patients with chemorefractory metastatic colorectal cancer (CRC). Nonetheless, selecting patients who are most likely to benefit from one specific therapy is challenging owing to a lack of direct comparisons of the efficacy of these agents in specific settings. In this Review, the authors summarize the available evidence on the efficacy and safety of later-line therapies for patients with advanced-stage CRC and suggest an evidence-based treatment-selection algorithm.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 1","pages":"28-45"},"PeriodicalIF":81.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665319","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":"Allogeneic chimeric antigen receptor cell therapies for cancer: progress made and remaining roadblocks","authors":"Caroline Diorio, David T. Teachey, Stephan A. Grupp","doi":"10.1038/s41571-024-00959-y","DOIUrl":"10.1038/s41571-024-00959-y","url":null,"abstract":"Chimeric antigen receptor (CAR) T cells are revolutionizing cancer therapy, particularly for haematological malignancies, conferring durable and sometimes curative responses in patients with advanced-stage disease. The CAR T cell products currently approved for clinical use are all autologous and are often effective; however, in patients who are lymphopenic and/or heavily pretreated with chemotherapy, autologous T cells can be difficult to harvest in sufficient numbers or have functional impairments that might ultimately render them less efficacious. Moreover, autologous products take several weeks to produce, and each product can be used in only one patient. By contrast, allogeneic CAR T cells can be produced for many patients using T cells from a single healthy donor, can be optimized for safety and efficacy, can be instantly available for ‘off-the-shelf’ use and, therefore, might also be more cost-effective. Despite these potential advantages, the development of allogeneic CAR T cells has lagged behind that of autologous products, owing to the additional challenges such as avoiding graft-versus-host disease and host-mediated graft rejection. Over the past few years, the development of advanced genome-editing techniques has facilitated the generation of novel allogeneic CAR T cell products. Furthermore, CAR cell products derived from other cell types such as induced pluripotent stem cells and natural killer cells are being investigated for clinical use. In this Review, we discuss the potential of allogeneic CAR cell products to expand life-saving immunotherapy to a much broader population of patients in the coming years, the progress made to date and strategies to overcome remaining hurdles. Several chimeric antigen receptor (CAR) T cell therapies are approved for the treatment of various haematological cancers; however, they are all autologous products requiring individualized manufacturing for each patient, which presents technical, logistical and resource challenges that limits scalability and implementation, and even raises certain ethical questions. Allogeneic products have the potential to address many of these issues, but come with their own challenges. This Review summarizes the advantages and disadvantages of allogeneic CAR cell products derived from T cells or other immune cells, their engineering and progress towards clinical implementation, as well as hurdles that remain to be overcome.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 1","pages":"10-27"},"PeriodicalIF":81.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637134","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":"First-line triplet therapy for advanced-stage PIK3CA-mutant HR+ breast cancer improves outcomes","authors":"David Killock","doi":"10.1038/s41571-024-00968-x","DOIUrl":"10.1038/s41571-024-00968-x","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 1","pages":"1-1"},"PeriodicalIF":81.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599401","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":"Expanding the use of T-DXd in metastatic HR-positive breast cancer: where are we now?","authors":"Joshua Drago, Shanu Modi","doi":"10.1038/s41571-024-00963-2","DOIUrl":"10.1038/s41571-024-00963-2","url":null,"abstract":"The DESTINY-Breast06 trial investigated earlier and broader use of trastuzumab deruxtecan in patients with metastatic hormone-receptor-positive breast cancer, and demonstrated improvements in progression-free survival over standard chemotherapy. These data provide a meaningful advance; however, this strategy might not be right for all patients, and careful consideration is recommended before blanket use.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 1","pages":"6-7"},"PeriodicalIF":81.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588704","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":"On the cusp of targeted therapy for cancer cachexia — what clinical benefits might we promise our patients?","authors":"Vickie E. Baracos","doi":"10.1038/s41571-024-00964-1","DOIUrl":"10.1038/s41571-024-00964-1","url":null,"abstract":"A number of therapeutics that target mediators of signalling in the hypothalamic and brainstem regions that control appetite, ingestive behaviour, satiety, nausea and vomiting are starting to move the needle on cancer cachexia. However, clarification of meaningful clinical benefits for patients and the primary end points that should support regulatory approval of cachexia treatments is needed.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 1","pages":"8-9"},"PeriodicalIF":81.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580740","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":"Navigating the changing landscape of BTK-targeted therapies for B cell lymphomas and chronic lymphocytic leukaemia","authors":"Michele D. Stanchina, Skye Montoya, Alexey V. Danilov, Jorge J. Castillo, Alvaro J. Alencar, Julio C. Chavez, Chan Y. Cheah, Carlos Chiattone, Yucai Wang, Meghan Thompson, Paolo Ghia, Justin Taylor, Juan Pablo Alderuccio","doi":"10.1038/s41571-024-00956-1","DOIUrl":"10.1038/s41571-024-00956-1","url":null,"abstract":"The B cell receptor (BCR) signalling pathway has an integral role in the pathogenesis of many B cell malignancies, including chronic lymphocytic leukaemia, mantle cell lymphoma, diffuse large B cell lymphoma and Waldenström macroglobulinaemia. Bruton tyrosine kinase (BTK) is a key node mediating signal transduction downstream of the BCR. The advent of BTK inhibitors has revolutionized the treatment landscape of B cell malignancies, with these agents often replacing highly intensive and toxic chemoimmunotherapy regimens as the standard of care. In this Review, we discuss the pivotal trials that have led to the approval of various covalent BTK inhibitors, the current treatment indications for these agents and mechanisms of resistance. In addition, we discuss novel BTK-targeted therapies, including covalent, as well as non-covalent, BTK inhibitors, BTK degraders and combination doublet and triplet regimens, to provide insights on the best current treatment paradigms in the frontline setting and at disease relapse. In several B cell malignancies, BTK is a crucial mediator of oncogenic signalling pathways and inhibitors of this kinase have substantially improved patient outcomes. This Review discusses the currently approved indications for covalent and non-covalent BTK inhibitors, as well as mechanisms of resistance, and novel BTK-targeted agents and treatment strategies that have the potential to further improve outcomes.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 12","pages":"867-887"},"PeriodicalIF":81.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562057","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":"Author Correction: The high costs of anticancer therapies in the USA: challenges, opportunities and progress","authors":"Shelley A. Jazowski, Rahul K. Nayak, Stacie B. Dusetzina","doi":"10.1038/s41571-024-00958-z","DOIUrl":"10.1038/s41571-024-00958-z","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 12","pages":"903-903"},"PeriodicalIF":81.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41571-024-00958-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536890","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}