Nature Reviews Clinical Oncology最新文献

{"title":"International approvals of cilta-cel: a lens on CAR T cell regulation","authors":"Chenghao Ge, Chen Yin, Xiaoyuan Chen","doi":"10.1038/s41571-025-00996-1","DOIUrl":"10.1038/s41571-025-00996-1","url":null,"abstract":"The BCMA-targeted chimeric antigen receptor (CAR) T cell therapy ciltacabtagene autoleucel (cilta-cel) has demonstrated exceptional efficacy in studies conducted worldwide, which has resulted in regulatory approvals in >40 countries. Herein, we examine the regulatory pathways that led to its approval in different regions, focus on challenges in clinical development and regulatory submission, and provide insight into strategies for advancing innovative cell therapies.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"233-234"},"PeriodicalIF":81.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257964","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":"Hiding in plain sight: NUT carcinoma is an unrecognized subtype of squamous cell carcinoma of the lungs and head and neck","authors":"Jia Luo, Justin A. Bishop, Steven G. DuBois, Glenn J. Hanna, Lynette M. Sholl, Edward B. Stelow, Lester D. R. Thompson, Geoffrey I. Shapiro, Christopher A. French","doi":"10.1038/s41571-025-00986-3","DOIUrl":"10.1038/s41571-025-00986-3","url":null,"abstract":"In the past two decades, treatment for non-small-cell lung cancers (NSCLCs) and head and neck squamous cell carcinoma (HNSCC) has advanced considerably, owing largely to the characterization of distinct oncological subtypes, the development of targeted therapies for each subtype and the advent of immunotherapy. Data emerging over the past two decades suggest that NUT carcinoma, a highly aggressive malignancy driven by a NUT fusion oncoprotein and arising in the lungs, head and neck, and rarely in other sites, is a squamous cell carcinoma (SCC) based on transcriptional, histopathological, cell-of-origin and molecular characteristics. NUT carcinoma has an estimated incidence of 1,400 cases per year in the United States, surpassing that of some rare NSCLC and HNSCC subtypes. However, NUT carcinoma is currently not recognized as an SCC of the lungs or head and neck. The orphan classification of NUT carcinoma as a distinct entity leads to a lack of awareness of this malignancy among oncologists and surgeons, despite early diagnosis being crucial for this cancer type with a median survival of only ~6.5 months. Consequently, NUT carcinoma is underdiagnosed and often misdiagnosed, resulting in limited research and progress in developing effective treatments in one of the most aggressive forms of lung and head and neck cancer. With a growing number of targeted agents that can potentially be used to treat NUT carcinoma, improved recognition through reclassification and inclusion of NUT carcinoma as a squamous NSCLC or an HNSCC when arising in these locations will accelerate the development of effective therapies for this disease. Thus, in the Perspective, we propose such a reclassification of NUT carcinoma as an SCC and discuss the supporting evidence. Accumulating evidence indicates that NUT carcinoma, a highly aggressive malignancy driven by NUTM1 fusions, is a rare form of squamous cell carcinoma (SCC) of the lung or head and neck, calling into question its current classification as an entirely distinct disease entity. In this Perspective, the authors propose the reclassification of NUT carcinoma as an SCC, the supporting rationale, and the immediate implications for clinical practice and research","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"292-306"},"PeriodicalIF":81.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083319","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":"Perioperative chemotherapy superior to preoperative chemoradiotherapy for locally advanced EAC","authors":"David Killock","doi":"10.1038/s41571-025-00995-2","DOIUrl":"10.1038/s41571-025-00995-2","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"237-237"},"PeriodicalIF":81.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071853","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":"Thermal ablation is safer than resection of colorectal liver lesions","authors":"Diana Romero","doi":"10.1038/s41571-025-00994-3","DOIUrl":"10.1038/s41571-025-00994-3","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 3","pages":"158-158"},"PeriodicalIF":81.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056197","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":"Transforming paediatric AML trials: from failing one-size-fits-all methods to precision oncology","authors":"Branko Cuglievan, Vivek Subbiah","doi":"10.1038/s41571-025-00989-0","DOIUrl":"10.1038/s41571-025-00989-0","url":null,"abstract":"Paediatric acute myeloid leukaemia (AML) highlights the challenges of drug development for rare diseases, in which limited patient numbers and substantial heterogeneity hinder progress. Traditional one-size-fits-all randomized trials are ineffective. Nonetheless, tailored therapies and biomarker-driven studies can improve outcomes and transform the treatment of paediatric patients with AML and potentially other rare cancers.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 3","pages":"155-156"},"PeriodicalIF":81.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049697","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 addition of an ICI and an anti-angiogenic to TACE","authors":"Diana Romero","doi":"10.1038/s41571-025-00990-7","DOIUrl":"10.1038/s41571-025-00990-7","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 3","pages":"157-157"},"PeriodicalIF":81.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049986","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 intervention with daratumumab improves survival for patients with high-risk smouldering myeloma","authors":"Omar Nadeem, Irene M. Ghobrial","doi":"10.1038/s41571-025-00987-2","DOIUrl":"10.1038/s41571-025-00987-2","url":null,"abstract":"Recent results from the phase III AQUILA trial demonstrate the benefit of fixed-duration monotherapy with daratumumab over observation in patients with high-risk smouldering multiple myeloma, which changes the early interception treatment landscape. Herein, we discuss how future studies could build on this success and pave the way to eradicating multiple myeloma before it starts.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 3","pages":"159-160"},"PeriodicalIF":81.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026314","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":"Adding brentuximab vedotin to lenalidomide and rituximab improves OS in R/R DLBCL","authors":"David Killock","doi":"10.1038/s41571-025-00988-1","DOIUrl":"10.1038/s41571-025-00988-1","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 3","pages":"158-158"},"PeriodicalIF":81.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990883","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":"Circulating tumour DNA in early stage and locally advanced NSCLC: ready for clinical implementation?","authors":"Nicola Normanno, Alessandro Morabito, Anna Maria Rachiglio, Vincenzo Sforza, Lorenza Landi, Emilio Bria, Angelo Delmonte, Federico Cappuzzo, Antonella De Luca","doi":"10.1038/s41571-024-00985-w","DOIUrl":"10.1038/s41571-024-00985-w","url":null,"abstract":"Circulating tumour DNA (ctDNA) can be released by cancer cells into biological fluids through apoptosis, necrosis or active release. In patients with non-small-cell lung cancer (NSCLC), ctDNA levels correlate with clinical and pathological factors, including histology, tumour size and proliferative status. Currently, ctDNA analysis is recommended for molecular profiling in patients with advanced-stage NSCLC. In this Review, we summarize the increasing evidence suggesting that ctDNA has potential clinical applications in the management of patients with early stage and locally advanced NSCLC. In those with early stage NSCLC, detection of ctDNA before and/or after surgery is associated with a greater risk of disease recurrence. Longitudinal monitoring after surgery can further increase the prognostic value of ctDNA testing and enables detection of disease recurrence earlier than the assessment of clinical or radiological progression. In patients with locally advanced NSCLC, the detection of ctDNA after chemoradiotherapy is also associated with a greater risk of disease progression. Owing to the limited number of patients enrolled and the different technologies used for ctDNA testing in most of the clinical studies performed thus far, their results are not sufficient to currently support the routine clinical use of ctDNA monitoring in patients with early stage or locally advanced NSCLC. Therefore, we discuss the need for interventional studies to provide evidence for implementing ctDNA testing in this setting. Analysis of circulating tumour DNA (ctDNA) is commonly used for molecular profiling in patients with advanced-stage non-small-cell lung cancer (NSCLC). The authors of this Review summarize the available evidence on the potential utility of incorporating ctDNA in the management of those with early stage and locally advanced NSCLC and propose interventional studies to provide the necessary additional evidence.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 3","pages":"215-231"},"PeriodicalIF":81.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990884","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":"Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach","authors":"Miguel Lopez de Rodas, Maria Villalba-Esparza, Miguel F. Sanmamed, Lieping Chen, David L. Rimm, Kurt A. Schalper","doi":"10.1038/s41571-024-00984-x","DOIUrl":"10.1038/s41571-024-00984-x","url":null,"abstract":"Immune-checkpoint inhibitors (ICIs) have improved clinical outcomes across several solid tumour types. Prominent efforts have focused on understanding the anticancer mechanisms of these agents, identifying biomarkers of response and uncovering resistance mechanisms to develop new immunotherapeutic approaches. This research has underscored the crucial roles of the tumour microenvironment and, particularly, tumour-infiltrating lymphocytes (TILs) in immune-mediated tumour elimination. Numerous studies have evaluated the prognostic and predictive value of TILs and the mechanisms that govern T cell dysfunction, fuelled by technical developments in single-cell transcriptomics, proteomics, high-dimensional spatial platforms and advanced computational models. However, questions remain regarding the definition of TILs, optimal strategies to study them, specific roles of different TIL subpopulations and their clinical implications in different treatment contexts. Additionally, most studies have focused on the abundance of major TIL subpopulations but have not developed standardized quantification strategies or analysed other crucial aspects such as their functional profile, spatial distribution and/or arrangement, tumour antigen-reactivity, clonal diversity and heterogeneity. In this Review, we discuss a conceptual framework for the systematic study of TILs and summarize the evidence regarding their biological properties and biomarker potential for ICI therapy. We also highlight opportunities, challenges and strategies to support future developments in this field. Tumour-infiltrating lymphocytes (TILs) are crucial effectors of the anticancer immune response and are hypothesized to be key determinants the efficacy of immune-checkpoint inhibitors (ICIs). Herein, the authors review studies that have evaluated the roles of various TIL subsets as predictive biomarkers for ICIs, as well as opportunities, challenges and strategies for future research in this field.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 3","pages":"163-181"},"PeriodicalIF":81.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987426","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}