Nature Reviews Clinical Oncology最新文献

{"title":"Outcome correlates of approved CD19-targeted CAR T cells for large B cell lymphoma","authors":"Tamara J. Bock, Chanukya K. Colonne, Salvatore Fiorenza, Cameron J. Turtle","doi":"10.1038/s41571-025-00992-5","DOIUrl":"10.1038/s41571-025-00992-5","url":null,"abstract":"CD19-targeted chimeric antigen receptor (CAR) T cells have provided a breakthrough in the treatment of patients with relapsed and/or refractory large B cell lymphoma (LBCL). Currently, three CD19-targeted CAR T cell products are approved by the FDA and various other regulators for the treatment of patients with LBCL: axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel. Response rates following infusion of these CD19-targeted CAR T cells have been promising; however, approximately half of treated patients show relapse within 2 years. Furthermore, receiving these agents can be associated with serious toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. In this Review, we summarize the factors associated with the efficacy, including response and survival outcomes, and toxicity of CD19-targeted CAR T cells in pivotal clinical trials and large real-world datasets describing the outcomes of patients with LBCL who received treatment with these products. CD19-targeted CAR T cells have transformed the management of patients with relapsed and/or refractory large B cell lymphoma, and these therapies are increasingly being administered as earlier-line therapies. Nonetheless, the prognosis of these patients is often difficult to predict, with various prospective and real-world studies suggesting that a wide range of factors are associated with treatment outcomes. In this Review, the authors summarize these various associations as well as their implications for patient selection and management.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"241-261"},"PeriodicalIF":81.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435290","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":"Artificial intelligence in digital pathology — time for a reality check","authors":"Arpit Aggarwal, Satvika Bharadwaj, Germán Corredor, Tilak Pathak, Sunil Badve, Anant Madabhushi","doi":"10.1038/s41571-025-00991-6","DOIUrl":"10.1038/s41571-025-00991-6","url":null,"abstract":"The past decade has seen the introduction of artificial intelligence (AI)-based approaches aimed at optimizing several workflows across many medical specialties. In clinical oncology, the most promising applications include those involving image analysis, such as digital pathology. In this Perspective, we provide a comprehensive examination of the developments in AI in digital pathology between 2019 and 2024. We evaluate the current landscape from the lens of technological innovations, regulatory trends, deployment and implementation, reimbursement and commercial implications. We assess the technological advances that have driven improvements in AI, enabling more robust and scalable solutions for digital pathology. We also examine regulatory developments, in particular those affecting in-house devices and laboratory-developed tests, which are shaping the landscape of AI-based tools in digital pathology. Finally, we discuss the role of reimbursement frameworks and commercial investment in the clinical adoption of AI-based technologies. In this Perspective, we highlight both the progress and challenges in AI-driven digital pathology over the past 5 years, outlining the path forward for its adoption into routine practice in clinical oncology. The authors of this Perspective evaluate the developments in the use of artificial intelligence (AI) in digital pathology for oncology applications between 2019 and 2024, addressing technological innovations, regulatory trends, implementation and financial implications. Importantly, they explore the current landscape of clinical deployment, highlighting future opportunities for the integration of AI into clinical oncology routine practice.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"283-291"},"PeriodicalIF":81.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393110","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":"Intermediate-affinity CD19-directed CAR T cell product obecabtagene autoleucel demonstrates favourable safety and efficacy in R/R B-ALL","authors":"Rawan G. Faramand, Frederick L. Locke","doi":"10.1038/s41571-025-00993-4","DOIUrl":"10.1038/s41571-025-00993-4","url":null,"abstract":"Recent data from the FELIX trial evaluating obecabtagene autoleucel in patients with relapsed and/or refractory B acute lymphoblastic leukaemia (R/R B-ALL) suggest that this novel intermediate-affinity CD19-directed chimeric antigen receptor (CAR) T cell therapy is associated with a reduced incidence of severe immune-mediated toxicities compared with other commercially available CAR T cell products. The increasing number of therapies available for B-ALL makes treatment selection and sequencing of therapies increasingly challenging.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 3","pages":"161-162"},"PeriodicalIF":81.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375308","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":"AI accurately identifies targetable alterations in lung cancer histological images","authors":"Hortense Le, Aristotelis Tsirigos","doi":"10.1038/s41571-025-00999-y","DOIUrl":"10.1038/s41571-025-00999-y","url":null,"abstract":"DeepGEM, an artificial intelligence (AI)-based model, accurately predicts the presence of key genomic alterations in histological slides prepared from samples obtained from patients with lung cancer. This approach provides a cost-effective alternative to genomic testing, generates spatial mutation maps and might support personalized treatment strategies. Validated in diverse datasets, DeepGEM highlights the potential of AI to transform precision oncology and improve global healthcare equity.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"239-240"},"PeriodicalIF":81.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375171","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":"Cadonilimab is efficacious in HER2-negative advanced-stage G/GEJ adenocarcinomas","authors":"Diana Romero","doi":"10.1038/s41571-025-00998-z","DOIUrl":"10.1038/s41571-025-00998-z","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"237-237"},"PeriodicalIF":81.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367370","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":"Transanal TME noninferior to the laparoscopic approach","authors":"Peter Sidaway","doi":"10.1038/s41571-025-00997-0","DOIUrl":"10.1038/s41571-025-00997-0","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"237-237"},"PeriodicalIF":81.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258062","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":"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}