Pub Date : 2025-10-27DOI: 10.1038/s41571-025-01092-0
Diana Romero
{"title":"Belzutifan as a new option in pheochromocytomas and paragangliomas","authors":"Diana Romero","doi":"10.1038/s41571-025-01092-0","DOIUrl":"10.1038/s41571-025-01092-0","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 12","pages":"899-899"},"PeriodicalIF":82.2,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373812","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}
Pub Date : 2025-10-09DOI: 10.1038/s41571-025-01080-4
Jordi Remon, Antonin Levy, Romane Gille, Isabelle Martel-Lafay, Martina Bortolot, Lizza E. L. Hendriks, Corinne Faivre-Finn, Natasha Leighl, Martin Reck, Maurice Pérol
Despite advances in immunotherapy, unresectable stage III non-small-cell lung cancer (NSCLC) remains a highly challenging disease, with only around one-third of patients remaining disease-free at 5 years. The PACIFIC trial established consolidation with the anti-PD-L1 antibody durvalumab after concurrent chemoradiotherapy as the standard-of-care approach. Furthermore, the LAURA trial has redefined the treatment of patients with stage III unresectable EGFR-mutant NSCLC, demonstrating unprecedented progression-free survival durations with osimertinib consolidation. Despite these advances, novel approaches are urgently needed. Circulating tumour DNA-based monitoring of minimal residual disease is emerging as a personalized method of tailoring treatment duration and escalation strategies. Novel radiotherapy techniques have the potential to provide synergy with immunotherapy while minimizing toxicities. Additionally, ongoing trials evaluating chemoimmunotherapy combinations adapted from the neoadjuvant setting with the potential for conversion to resectable disease might, in the near future, redefine the boundary of surgical resectability. In this Review, we describe the rapidly evolving field of unresectable stage III NSCLC, providing a state-of-the-art overview that includes challenging topics such as biomarkers, personalization of therapy and the role of immunotherapy rechallenge. Patients with unresectable stage III non-small-cell lung cancer without EGFR or ALK mutations typically receive the PACIFIC regimen — concurrent chemoradiotherapy (cCRT) followed by consolidation with durvalumab — whereas those with EGFR-mutant disease typically receive cCRT followed by an EGFR inhibitor. Nonetheless, a subset of patients within this heterogeneous group might be able to completely avoid consolidation therapy, whereas others are unable to tolerate cCRT. In this Review, the authors describe the standard-of-care approach in this setting, followed by discussions of treatment optimization for specific subgroups, as well as important future research questions.
{"title":"Unresectable stage III non-small-cell lung cancer: state of the art and challenges","authors":"Jordi Remon, Antonin Levy, Romane Gille, Isabelle Martel-Lafay, Martina Bortolot, Lizza E. L. Hendriks, Corinne Faivre-Finn, Natasha Leighl, Martin Reck, Maurice Pérol","doi":"10.1038/s41571-025-01080-4","DOIUrl":"10.1038/s41571-025-01080-4","url":null,"abstract":"Despite advances in immunotherapy, unresectable stage III non-small-cell lung cancer (NSCLC) remains a highly challenging disease, with only around one-third of patients remaining disease-free at 5 years. The PACIFIC trial established consolidation with the anti-PD-L1 antibody durvalumab after concurrent chemoradiotherapy as the standard-of-care approach. Furthermore, the LAURA trial has redefined the treatment of patients with stage III unresectable EGFR-mutant NSCLC, demonstrating unprecedented progression-free survival durations with osimertinib consolidation. Despite these advances, novel approaches are urgently needed. Circulating tumour DNA-based monitoring of minimal residual disease is emerging as a personalized method of tailoring treatment duration and escalation strategies. Novel radiotherapy techniques have the potential to provide synergy with immunotherapy while minimizing toxicities. Additionally, ongoing trials evaluating chemoimmunotherapy combinations adapted from the neoadjuvant setting with the potential for conversion to resectable disease might, in the near future, redefine the boundary of surgical resectability. In this Review, we describe the rapidly evolving field of unresectable stage III NSCLC, providing a state-of-the-art overview that includes challenging topics such as biomarkers, personalization of therapy and the role of immunotherapy rechallenge. Patients with unresectable stage III non-small-cell lung cancer without EGFR or ALK mutations typically receive the PACIFIC regimen — concurrent chemoradiotherapy (cCRT) followed by consolidation with durvalumab — whereas those with EGFR-mutant disease typically receive cCRT followed by an EGFR inhibitor. Nonetheless, a subset of patients within this heterogeneous group might be able to completely avoid consolidation therapy, whereas others are unable to tolerate cCRT. In this Review, the authors describe the standard-of-care approach in this setting, followed by discussions of treatment optimization for specific subgroups, as well as important future research questions.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 1","pages":"22-39"},"PeriodicalIF":82.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254780","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}
Pub Date : 2025-10-08DOI: 10.1038/s41571-025-01079-x
W. K. Jacky Lam, Brigette B. Y. Ma, Ann D. King, Yasine Malki, K. C. Allen Chan, Anthony T. C. Chan
Nasopharyngeal carcinoma (NPC) is a major disease burden in endemic regions, where Epstein–Barr virus (EBV) infection has a key aetiological role in this malignancy. Both plasma EBV DNA and serum antibodies targeting EBV antigens have been validated independently in large-scale prospective trials as effective biomarkers for early detection of NPC. Plasma EBV DNA analysis by PCR could identify patients with early-stage, asymptomatic NPC. Emergent studies have shown that fragmentomics analysis of plasma EBV DNA can further enhance the specificity of NPC detection at the time of testing and better predict the future risk of NPC. Initial antibody-based NPC screening approaches were based on the detection of immunoglobulin A antibodies targeting EBV viral capsid antigen or Epstein–Barr nuclear antigen 1, which resulted in a subsequent reduction in NPC-specific mortality in a population screening trial. Subsequently, the detection of anti-BNLF2b antibodies alone has been reported to achieve higher sensitivity and specificity relative to the dual antibody approach. Cost-effectiveness analyses support the implementation of NPC screening in endemic regions using either EBV DNA or antibodies. Ongoing research initiatives are focusing on developing prophylactic and therapeutic vaccines as preventive measures against EBV-associated diseases, including NPC. In this Review, we discuss these advances as well as their relevance for the implementation of prevention strategies such as population-wide NPC screening and vaccination in endemic areas of NPC prevalence. We also highlight valuable insights from plasma EBV DNA studies that might facilitate optimization of liquid biopsy-based screening strategies for other types of cancer. Epstein–Barr virus (EBV) infection has a key aetiological role in endemic nasopharyngeal carcinoma (NPC). The authors of this Review discuss advances in NPC screening, which leverage the detection of either plasma EBV DNA or serum antibodies targeting EBV antigens, as well as in prevention, which relies on prophylactic and therapeutic vaccines for NPC.
鼻咽癌（NPC）是流行地区的主要疾病负担，eb病毒（EBV）感染在这种恶性肿瘤中起着关键的病因学作用。血浆EBV DNA和针对EBV抗原的血清抗体已在大规模前瞻性试验中被独立验证为早期检测鼻咽癌的有效生物标志物。血浆EBV DNA PCR分析可鉴别早期无症状鼻咽癌患者。新兴研究表明，血浆EBV DNA片段组学分析可以进一步提高检测时鼻咽癌检测的特异性，更好地预测鼻咽癌的未来风险。最初基于抗体的鼻咽癌筛查方法是基于检测针对EBV病毒衣壳抗原或Epstein-Barr核抗原1的免疫球蛋白A抗体，这导致随后在人群筛查试验中降低了鼻咽癌特异性死亡率。随后，有报道称单独检测抗bnlf2b抗体比双抗体方法具有更高的灵敏度和特异性。成本效益分析支持在流行地区使用EBV DNA或抗体进行鼻咽癌筛查。正在开展的研究活动侧重于开发预防性和治疗性疫苗，作为预防ebv相关疾病（包括鼻咽癌）的措施。在这篇综述中，我们讨论了这些进展以及它们与实施预防策略的相关性，如在鼻咽癌流行的流行地区进行全民鼻咽癌筛查和疫苗接种。我们还强调了血浆EBV DNA研究的宝贵见解，这些研究可能有助于优化基于液体活检的其他类型癌症筛查策略。
{"title":"Achieving control of nasopharyngeal carcinoma: the role of Epstein–Barr virus-based screening and vaccines","authors":"W. K. Jacky Lam, Brigette B. Y. Ma, Ann D. King, Yasine Malki, K. C. Allen Chan, Anthony T. C. Chan","doi":"10.1038/s41571-025-01079-x","DOIUrl":"10.1038/s41571-025-01079-x","url":null,"abstract":"Nasopharyngeal carcinoma (NPC) is a major disease burden in endemic regions, where Epstein–Barr virus (EBV) infection has a key aetiological role in this malignancy. Both plasma EBV DNA and serum antibodies targeting EBV antigens have been validated independently in large-scale prospective trials as effective biomarkers for early detection of NPC. Plasma EBV DNA analysis by PCR could identify patients with early-stage, asymptomatic NPC. Emergent studies have shown that fragmentomics analysis of plasma EBV DNA can further enhance the specificity of NPC detection at the time of testing and better predict the future risk of NPC. Initial antibody-based NPC screening approaches were based on the detection of immunoglobulin A antibodies targeting EBV viral capsid antigen or Epstein–Barr nuclear antigen 1, which resulted in a subsequent reduction in NPC-specific mortality in a population screening trial. Subsequently, the detection of anti-BNLF2b antibodies alone has been reported to achieve higher sensitivity and specificity relative to the dual antibody approach. Cost-effectiveness analyses support the implementation of NPC screening in endemic regions using either EBV DNA or antibodies. Ongoing research initiatives are focusing on developing prophylactic and therapeutic vaccines as preventive measures against EBV-associated diseases, including NPC. In this Review, we discuss these advances as well as their relevance for the implementation of prevention strategies such as population-wide NPC screening and vaccination in endemic areas of NPC prevalence. We also highlight valuable insights from plasma EBV DNA studies that might facilitate optimization of liquid biopsy-based screening strategies for other types of cancer. Epstein–Barr virus (EBV) infection has a key aetiological role in endemic nasopharyngeal carcinoma (NPC). The authors of this Review discuss advances in NPC screening, which leverage the detection of either plasma EBV DNA or serum antibodies targeting EBV antigens, as well as in prevention, which relies on prophylactic and therapeutic vaccines for NPC.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"23 1","pages":"7-21"},"PeriodicalIF":82.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246767","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}
Pub Date : 2025-10-08DOI: 10.1038/s41571-025-01074-2
David W. Greening, Rong Xu, Alin Rai, Wittaya Suwakulsiri, Maoshan Chen, Richard J. Simpson
Extracellular vesicles (EVs) encompass a multitude of lipid bilayer-delimited particles, of which exosomes are the most widely studied. Bidirectional cell–cell communications via EVs have a pivotal role in the physiology of multicellular organisms. EVs carry biological cargoes (including proteins, RNA, DNA, lipids and metabolites) capable of mediating a range of pleiotropic cellular functions. Over the past decade, EVs released by cancer cells (onco-EVs) have been shown to promote cancer progression including tumour outgrowth and metastatic dissemination. Furthermore, the innate ability of EVs to protect vulnerable molecular cargoes (such as RNA, DNA or proteins) from enzymatic degradation, their presence in most biofluids and the ability to transverse biological barriers to reach distant organs make them ideal targeted drug delivery systems, including in patients with cancer. Many of these properties also support investigations of EVs as biomarkers with potential roles in both diagnosis and treatment monitoring. In this Review, we describe advances in the development of EVs as cancer therapeutics or biomarkers, including cancer vaccines, targeted drug delivery systems and immunotherapies, as well as potential roles in early cancer detection, diagnosis and clinical management. We also describe the potential of emerging technologies to support further discoveries as well as the clinical translation of EVs into diagnostic and therapeutic clinical tools. We highlight the potential of single-EV and onco-EV detection and discuss how advances in multi-omic and artificial intelligence-enabled integration are providing new biological insights and driving clinical translation. Extracellular vesicles (EVs), a diverse range of membrane-delimited particles, have multiple cellular functions and, when released by cancer cells, can promote tumour growth and metastatic dissemination. The authors of this Review describe advances in the development of EVs as biomarkers and cancer therapeutics, focusing on clinical translation of EVs into diagnostic and therapeutic clinical tools.
{"title":"Clinical relevance of extracellular vesicles in cancer — therapeutic and diagnostic potential","authors":"David W. Greening, Rong Xu, Alin Rai, Wittaya Suwakulsiri, Maoshan Chen, Richard J. Simpson","doi":"10.1038/s41571-025-01074-2","DOIUrl":"10.1038/s41571-025-01074-2","url":null,"abstract":"Extracellular vesicles (EVs) encompass a multitude of lipid bilayer-delimited particles, of which exosomes are the most widely studied. Bidirectional cell–cell communications via EVs have a pivotal role in the physiology of multicellular organisms. EVs carry biological cargoes (including proteins, RNA, DNA, lipids and metabolites) capable of mediating a range of pleiotropic cellular functions. Over the past decade, EVs released by cancer cells (onco-EVs) have been shown to promote cancer progression including tumour outgrowth and metastatic dissemination. Furthermore, the innate ability of EVs to protect vulnerable molecular cargoes (such as RNA, DNA or proteins) from enzymatic degradation, their presence in most biofluids and the ability to transverse biological barriers to reach distant organs make them ideal targeted drug delivery systems, including in patients with cancer. Many of these properties also support investigations of EVs as biomarkers with potential roles in both diagnosis and treatment monitoring. In this Review, we describe advances in the development of EVs as cancer therapeutics or biomarkers, including cancer vaccines, targeted drug delivery systems and immunotherapies, as well as potential roles in early cancer detection, diagnosis and clinical management. We also describe the potential of emerging technologies to support further discoveries as well as the clinical translation of EVs into diagnostic and therapeutic clinical tools. We highlight the potential of single-EV and onco-EV detection and discuss how advances in multi-omic and artificial intelligence-enabled integration are providing new biological insights and driving clinical translation. Extracellular vesicles (EVs), a diverse range of membrane-delimited particles, have multiple cellular functions and, when released by cancer cells, can promote tumour growth and metastatic dissemination. The authors of this Review describe advances in the development of EVs as biomarkers and cancer therapeutics, focusing on clinical translation of EVs into diagnostic and therapeutic clinical tools.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 12","pages":"924-952"},"PeriodicalIF":82.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246766","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}
Pub Date : 2025-10-03DOI: 10.1038/s41571-025-01077-z
Heng-Chung Kung, Kevin W. Zheng, Jacquelyn W. Zimmerman, Lei Zheng
Patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) predominantly receive chemotherapy, and despite initial responses in some patients, most will have disease progression and often dismal outcomes. This lack of clinical effectiveness partly reflects not only cancer cell-intrinsic factors but also the presence of a tumour microenvironment (TME) that precludes access of both systemic therapies and circulating immune cells to the primary tumour, as well as supporting the growth of PDAC cells. Combined with improved preclinical models of PDAC, advances in single-cell spatial multi-omics and machine learning-based models have provided novel methods of untangling the complexities of the TME. In this Review, we focus on the desmoplastic stroma and both the intratumoural and intertumoural heterogeneity of PDAC, with an emphasis on cancer-associated fibroblasts and their surrounding immune cell niches. We describe new approaches in converting the immunologically ‘cold’ PDAC TME into a ‘hot’ TME by priming T cell activation, overcoming T cell exhaustion and unravelling myeloid cell-mediated immunosuppression. Furthermore, we explore integrated targets involving the TME, such as points of convergence among tumour, stromal and immune cell metabolism as well as oncogenic KRAS signalling. Finally, building on our experience with failed clinical trials in the past, we consider how this evolving comprehensive understanding of the TME will ensure future success in developing more effective therapies for patients with PDAC. Patients with advanced-stage pancreatic ductal adenocarcinoma often have dismal outcomes, despite an initial response sometimes to standard-of-care chemotherapy. This treatment refractoriness partly reflects the effects of the tumour microenvironment (TME), which is highly heterogeneous but can include a dense desmoplastic stroma as well as various immune cell and cancer-associated fibroblast populations, most of which collectively promote resistance to treatment and disease progression. In this Review, the authors summarize the role of the TME in determining the outcomes of patients with pancreatic ductal adenocarcinoma, and consider novel therapeutic approaches that might promote the development of a tumour-suppressive TME.
{"title":"The tumour microenvironment in pancreatic cancer — new clinical challenges, but more opportunities","authors":"Heng-Chung Kung, Kevin W. Zheng, Jacquelyn W. Zimmerman, Lei Zheng","doi":"10.1038/s41571-025-01077-z","DOIUrl":"10.1038/s41571-025-01077-z","url":null,"abstract":"Patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) predominantly receive chemotherapy, and despite initial responses in some patients, most will have disease progression and often dismal outcomes. This lack of clinical effectiveness partly reflects not only cancer cell-intrinsic factors but also the presence of a tumour microenvironment (TME) that precludes access of both systemic therapies and circulating immune cells to the primary tumour, as well as supporting the growth of PDAC cells. Combined with improved preclinical models of PDAC, advances in single-cell spatial multi-omics and machine learning-based models have provided novel methods of untangling the complexities of the TME. In this Review, we focus on the desmoplastic stroma and both the intratumoural and intertumoural heterogeneity of PDAC, with an emphasis on cancer-associated fibroblasts and their surrounding immune cell niches. We describe new approaches in converting the immunologically ‘cold’ PDAC TME into a ‘hot’ TME by priming T cell activation, overcoming T cell exhaustion and unravelling myeloid cell-mediated immunosuppression. Furthermore, we explore integrated targets involving the TME, such as points of convergence among tumour, stromal and immune cell metabolism as well as oncogenic KRAS signalling. Finally, building on our experience with failed clinical trials in the past, we consider how this evolving comprehensive understanding of the TME will ensure future success in developing more effective therapies for patients with PDAC. Patients with advanced-stage pancreatic ductal adenocarcinoma often have dismal outcomes, despite an initial response sometimes to standard-of-care chemotherapy. This treatment refractoriness partly reflects the effects of the tumour microenvironment (TME), which is highly heterogeneous but can include a dense desmoplastic stroma as well as various immune cell and cancer-associated fibroblast populations, most of which collectively promote resistance to treatment and disease progression. In this Review, the authors summarize the role of the TME in determining the outcomes of patients with pancreatic ductal adenocarcinoma, and consider novel therapeutic approaches that might promote the development of a tumour-suppressive TME.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 12","pages":"969-995"},"PeriodicalIF":82.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215629","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}
Pub Date : 2025-10-03DOI: 10.1038/s41571-025-01083-1
Alireza Mansouri, Ahmad Ozair, Debarati Bhanja, Hannah Wilding, Elad Mashiach, Waqas Haque, Nicholas Mikolajewicz, Leonardo de Macedo Filho, Sean S. Mahase, Mitchell Machtay, Philippe Metellus, Frédéric Dhermain, Jason Sheehan, Douglas Kondziolka, L. Dade Lunsford, Ajay Niranjan, Giuseppe Minniti, Jing Li, Steven N. Kalkanis, Patrick Y. Wen, Rupesh Kotecha, Michael W. McDermott, Chetan Bettegowda, Graeme F. Woodworth, Paul D. Brown, Arjun Sahgal, Manmeet S. Ahluwalia
{"title":"Author Correction: Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care","authors":"Alireza Mansouri, Ahmad Ozair, Debarati Bhanja, Hannah Wilding, Elad Mashiach, Waqas Haque, Nicholas Mikolajewicz, Leonardo de Macedo Filho, Sean S. Mahase, Mitchell Machtay, Philippe Metellus, Frédéric Dhermain, Jason Sheehan, Douglas Kondziolka, L. Dade Lunsford, Ajay Niranjan, Giuseppe Minniti, Jing Li, Steven N. Kalkanis, Patrick Y. Wen, Rupesh Kotecha, Michael W. McDermott, Chetan Bettegowda, Graeme F. Woodworth, Paul D. Brown, Arjun Sahgal, Manmeet S. Ahluwalia","doi":"10.1038/s41571-025-01083-1","DOIUrl":"10.1038/s41571-025-01083-1","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 12","pages":"996-996"},"PeriodicalIF":82.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41571-025-01083-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225724","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}
Pub Date : 2025-10-02DOI: 10.1038/s41571-025-01075-1
Jiarui Li, Chang Liu, Panpan Zhang, Lin Shen, Changsong Qi
Chimeric antigen receptor (CAR) T cell therapy is revolutionizing the management of haematological malignancies but faces particular hurdles in the treatment of solid tumours. In this Review, we discuss important advances in refining CAR T cell therapy to provide practical clinical insights to address these challenges. We describe key strategies, including target antigen selection to enhance efficacy while minimizing on-target, off-tumour toxicities; early apheresis, rapid manufacturing and frontline application to preserve T cell fitness and ensure timely treatment; lymphodepletion to augment CAR T cell expansion; locoregional delivery to maximize local therapeutic concentrations and reduce systemic toxicity; and repeat infusions to prolong therapeutic effects. Furthermore, we discuss advanced response evaluation frameworks that will be essential for accurate assessment of the efficacy of CAR T cell therapies, and we highlight the need for robust toxicity management approaches to mitigate severe adverse events. By systematically addressing these multifaceted challenges, this Review provides a comprehensive guide for the optimization of CAR T cell therapy for solid tumours to enhance both efficacy and safety. Chimeric antigen receptor (CAR) T cell therapy is revolutionizing the treatment of haematological malignancies, but expanding applicability to solid tumours presents substantial challenges. This Review describes key strategies to optimize CAR T cell therapy for solid tumours across areas spanning from target selection to response and safety evaluation.
{"title":"Optimizing CAR T cell therapy for solid tumours: a clinical perspective","authors":"Jiarui Li, Chang Liu, Panpan Zhang, Lin Shen, Changsong Qi","doi":"10.1038/s41571-025-01075-1","DOIUrl":"10.1038/s41571-025-01075-1","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy is revolutionizing the management of haematological malignancies but faces particular hurdles in the treatment of solid tumours. In this Review, we discuss important advances in refining CAR T cell therapy to provide practical clinical insights to address these challenges. We describe key strategies, including target antigen selection to enhance efficacy while minimizing on-target, off-tumour toxicities; early apheresis, rapid manufacturing and frontline application to preserve T cell fitness and ensure timely treatment; lymphodepletion to augment CAR T cell expansion; locoregional delivery to maximize local therapeutic concentrations and reduce systemic toxicity; and repeat infusions to prolong therapeutic effects. Furthermore, we discuss advanced response evaluation frameworks that will be essential for accurate assessment of the efficacy of CAR T cell therapies, and we highlight the need for robust toxicity management approaches to mitigate severe adverse events. By systematically addressing these multifaceted challenges, this Review provides a comprehensive guide for the optimization of CAR T cell therapy for solid tumours to enhance both efficacy and safety. Chimeric antigen receptor (CAR) T cell therapy is revolutionizing the treatment of haematological malignancies, but expanding applicability to solid tumours presents substantial challenges. This Review describes key strategies to optimize CAR T cell therapy for solid tumours across areas spanning from target selection to response and safety evaluation.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 12","pages":"953-968"},"PeriodicalIF":82.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209080","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}
Pub Date : 2025-09-26DOI: 10.1038/s41571-025-01082-2
David Killock
{"title":"ALASCCA: an aspirin a day keeps colorectal cancer away","authors":"David Killock","doi":"10.1038/s41571-025-01082-2","DOIUrl":"10.1038/s41571-025-01082-2","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 11","pages":"801-801"},"PeriodicalIF":82.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153355","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}
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