Nature Reviews Clinical Oncology最新文献

{"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":"https://doi.org/10.1038/s41571-024-00965-0","url":null,"abstract":"<p>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 KRAS^G12C 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.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"10 1","pages":""},"PeriodicalIF":78.8,"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":"https://doi.org/10.1038/s41571-024-00959-y","url":null,"abstract":"<p>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.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"36 1","pages":""},"PeriodicalIF":78.8,"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":"Sacituzumab govitecan improves OS in heavily pretreated patients","authors":"Peter Sidaway","doi":"10.1038/s41571-023-00818-2","DOIUrl":"10.1038/s41571-023-00818-2","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"20 11","pages":"734-734"},"PeriodicalIF":78.8,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185568","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":"Early promising results with the novel KRASG12C inhibitor divarasib","authors":"Diana Romero","doi":"10.1038/s41571-023-00817-3","DOIUrl":"10.1038/s41571-023-00817-3","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"20 11","pages":"733-733"},"PeriodicalIF":78.8,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169425","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":"TAM family kinases as therapeutic targets at the interface of cancer and immunity","authors":"Deborah DeRyckere,&nbsp;Justus M. Huelse,&nbsp;H. Shelton Earp,&nbsp;Douglas K. Graham","doi":"10.1038/s41571-023-00813-7","DOIUrl":"10.1038/s41571-023-00813-7","url":null,"abstract":"Novel treatment approaches are needed to overcome innate and acquired mechanisms of resistance to current anticancer therapies in cancer cells and the tumour immune microenvironment. The TAM (TYRO3, AXL and MERTK) family receptor tyrosine kinases (RTKs) are potential therapeutic targets in a wide range of cancers. In cancer cells, TAM RTKs activate signalling pathways that promote cell survival, metastasis and resistance to a variety of chemotherapeutic agents and targeted therapies. TAM RTKs also function in innate immune cells, contributing to various mechanisms that suppress antitumour immunity and promote resistance to immune-checkpoint inhibitors. Therefore, TAM antagonists provide an unprecedented opportunity for both direct and immune-mediated therapeutic activity provided by inhibition of a single target, and are likely to be particularly effective when used in combination with other cancer therapies. To exploit this potential, a variety of agents have been designed to selectively target TAM RTKs, many of which have now entered clinical testing. This Review provides an essential guide to the TAM RTKs for clinicians, including an overview of the rationale for therapeutic targeting of TAM RTKs in cancer cells and the tumour immune microenvironment, a description of the current preclinical and clinical experience with TAM inhibitors, and a perspective on strategies for continued development of TAM-targeted agents for oncology applications. The TAM (TYRO3, AXL and MERTK) family receptor tyrosine kinases (RTKs) have diverse cancer-promoting functions in malignant cells as well as immune cells and other cell types in the tumour microenvironment, presenting an attractive opportunity for both direct and immune-mediated therapeutic activity manifest through inhibition of a single target. Accordingly, a variety of agents designed to selectively target TAM RTKs are entering clinical testing. This Review provides an essential guide to the TAM RTKs for clinicians. The authors comprehensively review the various roles of TAM RTKs in cancer, the evidence supporting their potential as therapeutic targets, and the translational development of TAM-targeted agents as cancer treatments.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"20 11","pages":"755-779"},"PeriodicalIF":78.8,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10507764","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":"Harnessing potent therapies with care: enfortumab vedotin plus pembrolizumab for advanced-stage urothelial carcinoma","authors":"Pooja Ghatalia,&nbsp;Elizabeth R. Plimack","doi":"10.1038/s41571-023-00814-6","DOIUrl":"10.1038/s41571-023-00814-6","url":null,"abstract":"Following the recent FDA Accelerated Approval of enfortumab vedotin (EV) plus pembrolizumab for patients with advanced-stage urothelial carcinoma who are cisplatin-ineligible, herein we highlight key clinical outcomes with this combination based on results from Cohort K of the pivotal phase&nbsp;Ib/II EV-103 trial. We also discuss treatment sequencing, de-escalation strategies and toxicity management as EV–pembrolizumab becomes widely used in clinical practice.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"20 12","pages":"818-819"},"PeriodicalIF":78.8,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10526700","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":"Emerging therapeutics and evolving assessment criteria for intracranial metastases in patients with oncogene-driven non-small-cell lung cancer","authors":"Kelsey Pan,&nbsp;Kyle Concannon,&nbsp;Jing Li,&nbsp;Jianjun Zhang,&nbsp;John V. Heymach,&nbsp;Xiuning Le","doi":"10.1038/s41571-023-00808-4","DOIUrl":"10.1038/s41571-023-00808-4","url":null,"abstract":"The improved survival outcomes of patients with non-small-cell lung cancer (NSCLC), largely owing to the improved control of systemic disease provided by immune-checkpoint inhibitors and novel targeted therapies, have highlighted the challenges posed by central nervous system (CNS) metastases as a devastating yet common complication, with up to 50% of patients developing such lesions during the course of the disease. Early-generation tyrosine-kinase inhibitors (TKIs) often provide robust systemic disease control in patients with oncogene-driven NSCLCs, although these agents are usually unable to accumulate to therapeutically relevant concentrations in the CNS owing to an inability to cross the blood–brain barrier. However, the past few years have seen a paradigm shift with the emergence of several novel or later-generation TKIs with improved CNS penetrance. Such agents have promising levels of activity against brain metastases, as demonstrated by data from preclinical and clinical studies. In this Review, we describe current preclinical and clinical evidence of the intracranial activity of TKIs targeting various oncogenic drivers in patients with NSCLC, with a focus on newer agents with enhanced CNS penetration, leptomeningeal disease and the need for intrathecal treatment options. We also discuss evolving assessment criteria and regulatory considerations for future clinical investigations. Despite improved outcomes owing to advances in systemic targeted therapies, patients with brain metastases from oncogene-driven non-small-cell lung cancer continue to have a poor prognosis. This situation largely reflects the limited central nervous system (CNS) penetrance of most targeted therapies, a limitation that is beginning to be addressed with the development of later-generation agents. In this Review, the authors describe the CNS activity of targeted therapies for patients with oncogene-driven non-small-cell lung cancers, including discussions of novel agents with improved CNS penetrance and the potential of intrathecal administration for patients with leptomeningeal disease.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"20 10","pages":"716-732"},"PeriodicalIF":78.8,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10077549","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":"Targeting cancer with mRNA–lipid nanoparticles: key considerations and future prospects","authors":"Edo Kon,&nbsp;Nitay Ad-El,&nbsp;Inbal Hazan-Halevy,&nbsp;Lior Stotsky-Oterin,&nbsp;Dan Peer","doi":"10.1038/s41571-023-00811-9","DOIUrl":"10.1038/s41571-023-00811-9","url":null,"abstract":"Harnessing mRNA–lipid nanoparticles (LNPs) to treat patients with cancer has been an ongoing research area that started before these versatile nanoparticles were successfully used as COVID-19 vaccines. Currently, efforts are underway to harness this platform for oncology therapeutics, mainly focusing on cancer vaccines targeting multiple neoantigens or direct intratumoural injections of mRNA–LNPs encoding pro-inflammatory cytokines. In this Review, we describe the opportunities of using mRNA–LNPs in oncology applications and discuss the challenges for successfully translating the findings of preclinical studies of these nanoparticles into the clinic. We critically appraise the potential of various mRNA–LNP targeting and delivery strategies, considering physiological, technological and manufacturing challenges. We explore these approaches in the context of the potential clinical applications best suited to each approach and highlight the obstacles that currently need to be addressed to achieve these applications. Finally, we provide insights from preclinical and clinical studies that are leading to this powerful platform being considered the next frontier in oncology treatment. In oncology, mRNA–lipid nanoparticles (LNPs) have been used either to achieve intratumoural expression of immune-stimulating cytokine combinations or as cancer vaccines, and new strategies are in development to enable the selective delivery of payloads into cancer cells previously considered unreachable. The authors of this Review present various approaches for delivering mRNA–LNPs to tumours and discuss improvements that will improve the selective targeting of cancer cells with mRNA–LNPs.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"20 11","pages":"739-754"},"PeriodicalIF":78.8,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41571-023-00811-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10011278","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":"Novel ICI–TKI combination improves HCC outcomes","authors":"David Killock","doi":"10.1038/s41571-023-00812-8","DOIUrl":"10.1038/s41571-023-00812-8","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"20 11","pages":"733-733"},"PeriodicalIF":78.8,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974648","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":"Adjuvant nivolumab shows promise in MCC","authors":"David Killock","doi":"10.1038/s41571-023-00810-w","DOIUrl":"10.1038/s41571-023-00810-w","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"20 11","pages":"734-734"},"PeriodicalIF":78.8,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10246784","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}