Cancer Cell最新文献

{"title":"Mechanisms of Progression of Myeloid Preleukemia to Transformed Myeloid Leukemia in Children with Down Syndrome.","authors":"Maurice Labuhn, Kelly Perkins, Sören Matzk, Leila Varghese, Catherine Garnett, Elli Papaemmanuil, Marlen Metzner, Alison Kennedy, Vyacheslav Amstislavskiy, Thomas Risch, Raj Bhayadia, David Samulowski, David Cruz Hernandez, Bilyana Stoilova, Valentina Iotchkova, Udo Oppermann, Carina Scheer, Kenichi Yoshida, Adrian Schwarzer, Jeffrey W Taub, John D Crispino, Mitchell J Weiss, Yasuhide Hayashi, Takashi Taga, Etsuro Ito, Seishi Ogawa, Dirk Reinhardt, Marie-Laure Yaspo, Peter J Campbell, Irene Roberts, Stefan N Constantinescu, Paresh Vyas, Dirk Heckl, Jan-Henning Klusmann","doi":"10.1016/j.ccell.2026.10.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.10.008","url":null,"abstract":"","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":""},"PeriodicalIF":56.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223363","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":"One structural class, one treatment? Firmonertinib in PACC-mutant NSCLC.","authors":"Derek De-Rui Huang, James Chih-Hsin Yang","doi":"10.1016/j.ccell.2026.08.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.08.003","url":null,"abstract":"<p><p>EGFR PACC-mutant non-small cell lung cancer (NSCLC) has limited treatment options. In this issue of Cancer Cell, Le et al. report preclinical profiles and promising systemic and intracranial efficacy of the broad-spectrum CNS-penetrant tyrosine kinase inhibitor firmonertinib in PACC-mutant NSCLC, supporting its further clinical development in this challenging mutation class.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":""},"PeriodicalIF":56.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206541","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":"Firmonertinib in advanced non-small cell lung cancer with epidermal growth factor receptor P-loop and αC-helix compressing mutations.","authors":"Xiuning Le, Jie Wang, Yan Yu, Yanqiu Zhao, David Planchard, Bo Gao, Alexander Spira, Jingling Liu, Xingya Li, Shirish Gadgeel, Natasha Leighl, Junqiang Zhang, Hidetoshi Hayashi, Makoto Nishio, Julien Mazieres, Adrianus Johannes de Langen, Maurice Pérol, Kiyotaka Yoh, Martin D Forster, Yasushi Goto, Maria de Miguel Luken, Fernando Fabio Franco Perez, Quincy Chu, Sagun Parakh, Monique B Nilsson, Yong Jiang, Tianhua Hu, Cunlin Wang, Nichole Baio, Luna Musib, Zineb Mounir, Marcin Kowanetz, Shirley Wang, Steven Yea, Jerry Hsu, Stuart Lutzker, John V Heymach, Oscar Juan-Vidal, Jonathan W Riess","doi":"10.1016/j.ccell.2026.09.011","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.09.011","url":null,"abstract":"<p><p>P-loop and αC-helix compressing (PACC) mutations comprise a structurally distinct subgroup of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) with limited treatment options. Firmonertinib is a once-daily oral, brain-penetrant, mutant-selective EGFR tyrosine kinase inhibitor with a unique trifluoroethoxy side chain. Firmonertinib had high anti-proliferative efficacy in EGFR PACC-mutant cells and xenografts. In the phase 1b FURTHER study (NCT05364073), patients with metastatic EGFR PACC-mutant NSCLC randomized to receive first-line firmonertinib 160 mg (n = 25) or 240 mg (n = 22) had confirmed objective response rates (ORRs) of 43% and 68%, median duration of response not reached and 14.6 months, and median progression-free survival of 11.1 and 16.0 months, respectively; treatment-related adverse events led to dose reductions (19% and 24%) and discontinuation (3% and 0%). Intracranial ORR among patients with brain metastases at baseline was 47% (8/17). Results support further study of first-line firmonertinib in patients with EGFR PACC-mutant NSCLC.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":""},"PeriodicalIF":56.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206577","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":"Beyond BMI: The diet-microbiome context of the obesity paradox.","authors":"En-Wei Tao, Jing-Yuan Fang, Ying-Xuan Chen","doi":"10.1016/j.ccell.2026.08.019","DOIUrl":"10.1016/j.ccell.2026.08.019","url":null,"abstract":"<p><p>In Nature, Desharnais et al. show that in diverse mouse models, anti-PD-1 sensitivity is more closely linked to the diet-microbiome-metabolite ecosystem than to obesity-associated metabolic dysfunction. Their findings reinforce body mass index (BMI) as an incomplete proxy for host biology and suggest strategies to improve anti-PD-1 efficacy without inducing obesity.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1933-1935"},"PeriodicalIF":56.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104584","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":"Microbial cues for a stem-like lymphoid niche","authors":"Ming Kuang","doi":"10.1016/j.ccell.2026.08.020","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.08.020","url":null,"abstract":"While tertiary lymphoid structures (TLSs) broadly correlate with immunotherapy efficacy, their functional heterogeneity can translate into divergent clinical outcomes. In this issue of Cancer Cell, Hu et al. uncover a microbiota-orchestrated stem-like lymphoid niche in which CD70+ ILC2s sustain progenitor exhausted T cells, and their findings redefine the functional organization underlying TLS-associated antitumor immunity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"8 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151872","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":"Hitting KRAS G12D without the gut punch: Can immunotherapy make it last?","authors":"Dae Won Kim,Ignacio Garrido-Laguna","doi":"10.1016/j.ccell.2026.09.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.09.009","url":null,"abstract":"In this issue of Cancer Cell, Shi et al. report encouraging early-phase results combining HRS-4642, an allele-specific KRAS G12D inhibitor, with the PD-L1 inhibitor adebrelimab in previously treated metastatic pancreatic cancer. The intravenous combination was safe and well tolerated, notably sparing patients the gastrointestinal toxicity common to oral KRAS inhibitors, and achieved a promising 43% response rate at the recommended dose.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"32 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151856","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":"Toward the next generation of CAR T cell therapies for cancer","authors":"Diren Usta,Crystal L. Mackall","doi":"10.1016/j.ccell.2026.09.005","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.09.005","url":null,"abstract":"With seven products approved by the US Food and Drug Administration (FDA) for 15 indications and more than 2,600 active clinical trials, chimeric antigen receptor (CAR) T cell therapy is firmly established as an effective therapeutic modality for cancer treatment, and promising early data demonstrate its potential in autoimmune diseases. Key challenges facing the field include extending efficacy to solid tumors and reducing the cost and complexity of manufacturing to improve patient access. In this review, we summarize the clinical lessons learned from the now substantial experience with commercial CAR T cells and clinical trials and discuss three waves shaping next-generation development: multi-engineered and logic-gated CAR T cells, rational combination strategies, and in vivo CAR T cell generation. By integrating clinical experience with emerging strategies, we highlight where CAR T cell therapy has succeeded, where current approaches remain insufficient, and how next-generation cell therapies may be designed to overcome these barriers.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"43 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151859","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":"Spatial omics resolves adrenergic and mesenchymal cell states in neuroblastoma","authors":"Anand G. Patel,Orr Ashenberg,Natalie B. Collins,Justina McEvoy,Melody Allensworth-James,Felipe Segato Dezem,Samantha Turk,Natalie Geiger,Arjumand Wani,Luke Zhang,Åsa Segerstolpe,Sizun Jiang,Cody Ramirez,Michal Slyper,Xin Huang,Chiara Caraccio,Hongjian Jin,Heather Sheppard,Meifen Lu,Ke Xu,Ti-Cheng Chang,Brent A. Orr,Selene Koo,Abbas Shirinifard,Chia-Wei Hsu,Richard H. Chapple,Amber Shen,Michael R. Clay,Ruth G. Tatevossian,Colleen Reilly,Jaimin Patel,Marybeth Lupo,Cynthia Cline,Danielle Dionne,Caroline B.M. Porter,Julia Waldman,Yunhao Bai,Bokai Zhu,Irving Barrera,Evan Murray,Sébastien Vigneau,Sara Napolitano,Isaac Wakiro,Jingyi Wu,Grace Grimaldi,Laura Dellostritto,Karla Helvie,Asaf Rotem,Ana Lako,Nicole Cullen,Kathleen L. Pfaff,Åsa Karlström,Judit Jané-Valbuena,Ellen Todres,Aaron Thorner,Paul Geeleher,Scott J. Rodig,Xin Zhou,Bruce E. Johnson,Gang Wu,Fei Chen,Jiyang Yu,Yury Goltsev,Jasmine Plummer,Garry P. Nolan,Orit Rozenblatt-Rosen,Haitao Pan,Aviv Regev,Elizabeth Stewart,Michael A. Dyer","doi":"10.1016/j.ccell.2026.09.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.09.008","url":null,"abstract":"Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage. Although cell lines derived from neuroblastoma patients have features of either adrenergic (ADRN) or mesenchymal (MES) cells, identifying MES cells in patient tumors is challenging and controversial. Here, to characterize intra- and inter-patient cellular heterogeneity, we analyze 54 neuroblastoma tumors spanning broad clinical, genetic, and histologic features using single-cell/single-nucleus RNA sequencing (sc/snRNA-seq), bulk RNA sequencing, spatial transcriptomics, and spatial proteomics. We show that tumor cells occupy distinct cellular neighborhoods separated from nonmalignant immune and stromal cells, yet established cell line-derived gene expression signatures fail to identify MES neuroblastoma cells. We therefore develop ADRN/MES signatures from early-passage orthotopic patient-derived xenografts, enabling the identification of MES tumor cells, validated by transcriptomic, epigenomic, proteomic, ultrastructural, and functional assays. In patients, high MES gene expression correlates with worse event-free and overall survival. Together, this study provides a framework for defining clinically relevant neuroblastoma cell states.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"11 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124069","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":"Chromatin plasticity and lineage repurposing: When gastric identity turns acidic","authors":"Xiaotian Zhang,Yakun Wang,Xiaoyi Chong,Jiabao Wang,Wenfei Li","doi":"10.1016/j.ccell.2026.09.010","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.09.010","url":null,"abstract":"Chromatin dynamics shape gastric cancer at every stage. In this issue of Cancer Cell, Wang et al. uncover a premalignant chromatin state primed for oncogenic activation alongside a pseudo-gastric subtype that hijacks acid secretion to evade antitumor immunity, revealing gastric proton pumps as a potential therapeutic target.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"628 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090101","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":"Chemotherapy enhances cancer vaccine efficacy and expands stem-like TCF1+CD8+ T cells","authors":"Laurine Noblecourt,Amanda Wicki,Ashwin Jainarayanan,Vinnycius Pereira-Almeida,James McAuliffe,Emily Steffke,Silvia Panetti,Hannah Fuchs,Ramiro A. Ramirez-Valdez,Vineethkrishna Chandrasekar,Yanshu Cai,Sanne Boekestijn,Adrian V.S. Hill,Audrey Gerard,Marij J.P. Welters,Sjoerd H. Van der Burg,Isabela Pedroza-Pacheco,Benoit J. Van den Eynde,Carol Sze Ki Leung","doi":"10.1016/j.ccell.2026.09.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.09.006","url":null,"abstract":"","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"17 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090139","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}