Cancer Cell最新文献_第2页

Restraint of cancer cell plasticity by spatial homotypic clustering 空间同型聚类对癌细胞可塑性的抑制

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-09-18 DOI: 10.1016/j.ccell.2025.08.009

Simona Migliozzi, Bruno Adabbo, Luciano Garofano, Fan Wu, Pedro Davila, Ricardo J. Komotar, Michael E. Ivan, Ashish H. Shah, Benjamin B. Currall, Sion Williams, Daniel Bilbao Cortes, Melinda Minucci Boone, Macarena I. de la Fuente, Sakir H. Gultekin, Michele Ceccarelli, Antonio Iavarone, Anna Lasorella

{"title":"Restraint of cancer cell plasticity by spatial homotypic clustering","authors":"Simona Migliozzi, Bruno Adabbo, Luciano Garofano, Fan Wu, Pedro Davila, Ricardo J. Komotar, Michael E. Ivan, Ashish H. Shah, Benjamin B. Currall, Sion Williams, Daniel Bilbao Cortes, Melinda Minucci Boone, Macarena I. de la Fuente, Sakir H. Gultekin, Michele Ceccarelli, Antonio Iavarone, Anna Lasorella","doi":"10.1016/j.ccell.2025.08.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.08.009","url":null,"abstract":"Tumor heterogeneity fueled by plasticity of cancer cells is a key to therapy failure. Here, we define the role of proximal communications of malignant cells in glioblastoma plasticity. We find that tumor cell state coherence is maximal in cells organized in homotypic clusters with defined relationships with non-malignant cells, whereas randomly dispersed cells downregulate the original state, acquire alternative phenotypes and exhibit changes in the microenvironment. We demonstrate the intrinsic propensity of glioblastoma cells to develop into clustered and dispersed spatial patterns in orthotopic mouse models and experimentally validate the cell state-specific mechanisms of cell-cell adhesion that prevent phenotype deviation with pharmacologic perturbations in patients-derived glioblastoma models. We establish the generality of “homotypic clustered cell identity” in circulating clustered and single breast cancer cells and show that the glioblastoma glycolytic-plurimetabolic dispersed cellular state uniquely confers shorter survival, thus assigning clinical significance to the spatial patterning of cancer cells in human tumors.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"77 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078556","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}

引用次数: 0

The coming era of nudge drugs for cancer 即将到来的助推抗癌药物时代

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-09-11 DOI: 10.1016/j.ccell.2025.08.004

Tristan Courau, Arpita Desai, Allon Wagner, Alexis J. Combes, Matthew F. Krummel

引用次数: 0

Protein-based classification reveals an immune-hot subtype in IDH mutant astrocytoma with worse prognosis 基于蛋白质的分类揭示了IDH突变型星形细胞瘤的免疫热亚型，预后较差

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-09-11 DOI: 10.1016/j.ccell.2025.08.006

Jihong Tang, Wenhua Fan, Yuyan Ruan, Xing Liu, Fufang Qiu, Jie Feng, Guoshi Huang, Mengli Yan, Hui Wang, Quanhua Mu, Ran Liu, Yingxi Yang, Zhi Huang, Yimeng Qiao, Xuejie Wang, Yumeng Guo, Mingchen Yu, Ying Zhang, Ruichao Chai, Fan Wu, Jiguang Wang

{"title":"Protein-based classification reveals an immune-hot subtype in IDH mutant astrocytoma with worse prognosis","authors":"Jihong Tang, Wenhua Fan, Yuyan Ruan, Xing Liu, Fufang Qiu, Jie Feng, Guoshi Huang, Mengli Yan, Hui Wang, Quanhua Mu, Ran Liu, Yingxi Yang, Zhi Huang, Yimeng Qiao, Xuejie Wang, Yumeng Guo, Mingchen Yu, Ying Zhang, Ruichao Chai, Fan Wu, Jiguang Wang","doi":"10.1016/j.ccell.2025.08.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.08.006","url":null,"abstract":"Intertumoral heterogeneity complicates treatment of IDH-mutant astrocytoma. We analyze spatiotemporal multi-omics data and discover four clusters: adipogenesis/fatty-acid-metabolism (AFM), proliferative/progenitor (PPR), immune/mesenchymal-enriched (IME), and neuronal (NEU). PPR and IME are associated with poorer prognosis, a result validated in The Cancer Genome Atlas (TCGA) and a Chinese cohort of 273 IDH-mutant astrocytomas. Longitudinal analysis of 189 initial-recurrent pairs shows an evolutionary shift toward PPR/IME subtypes. Mechanistically, PPR is enriched for CDKN2A/B deletions, whereas IME features increased gemistocytic differentiation (GD) and infiltration by exhausted T cells and plasma cells. Spatial multi-omics link GD morphology to mesenchymal-like (MES-like) tumor cell aggregates and lymphocyte-rich niches. MES-like tumor cells in IME overexpress interferon-stimulated genes such as GBP1, which we show promotes proliferation and migration. Finally, we develop an AI-powered classifier for patient stratification. Our work delineates protein-based clustering of IDH-mutant astrocytoma and reveals an immune-hot subgroup that may inform therapeutic development.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"67 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043279","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}

引用次数: 0

Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct patterns and potential markers of progression 胰腺导管内乳头状肿瘤的多组学分析揭示了不同的模式和潜在的进展标记

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-28 DOI: 10.1016/j.ccell.2025.08.001

Yuefan Wang, Tung-Shing M. Lih, Jae W. Lee, Takao Ohtsuka, Yuto Hozaka, Mari Mino-Kenudson, Nazmi Volkan Adsay, Claudio Luchini, Aldo Scarpa, Ajay V. Maker, Grace E. Kim, Jorge Paulino, Lijun Chen, Jongmin Woo, Liyuan Jiao, Zhenyu Sun, Davina Goodman, Michael J. Pflüger, Nicholas J. Roberts, Hanno Matthaei, Ralph H. Hruban

{"title":"Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct patterns and potential markers of progression","authors":"Yuefan Wang, Tung-Shing M. Lih, Jae W. Lee, Takao Ohtsuka, Yuto Hozaka, Mari Mino-Kenudson, Nazmi Volkan Adsay, Claudio Luchini, Aldo Scarpa, Ajay V. Maker, Grace E. Kim, Jorge Paulino, Lijun Chen, Jongmin Woo, Liyuan Jiao, Zhenyu Sun, Davina Goodman, Michael J. Pflüger, Nicholas J. Roberts, Hanno Matthaei, Ralph H. Hruban","doi":"10.1016/j.ccell.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.08.001","url":null,"abstract":"To enable early detection of pancreatic cancer from precancerous lesions, we analyze proteins and glycoproteins from 64 intraductal papillary mucinous neoplasms (IPMNs), 55 cyst fluid samples, 104 pancreatic ductal adenocarcinomas (PDACs), and various types of normal samples using mass spectrometry. High-grade IPMNs show enrichment of glycosylation level and tumor progression pathways compared to low-grade lesions. High-grade IPMN associated proteins, such as PLOD3, IRS2, LGALS9, and Trop-2, are identified and validated using immunolabeling and laser microdissection. Some high-grade associated proteins are also detected in pancreatic cyst fluids, which allows us to link proteins and glycoproteins expressed in neoplastic cells to clinically accessible biospecimens. Altered glycosylation level of extracellular matrix (ECM) proteins is observed in IPMNs compared to normal ducts. Additionally, we identify a subset of IPMNs with PDAC-like features, including elevated expression of ECM proteins. These findings offer insight into progression-associated proteins and emphasize the diagnostic and therapeutic potential of these proteins in pancreatic tumors.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"35 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911219","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}

引用次数: 0

Glioblastoma hijacks cholinergic networks 胶质母细胞瘤劫持胆碱能网络

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-28 DOI: 10.1016/j.ccell.2025.08.003

Yen Vu, Moran Amit

引用次数: 0

Phase 1/2 trial of encorafenib, cetuximab, and nivolumab in microsatellite stable BRAFV600E metastatic colorectal cancer 恩科非尼、西妥昔单抗和纳武单抗治疗微卫星稳定BRAFV600E转移性结直肠癌的1/2期试验

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-28 DOI: 10.1016/j.ccell.2025.08.002

Van K. Morris, Christine M. Parseghian, Vahid Bahrambeigi, Nourhan Abdelfattah, Lianchun Xiao, Anjali Agrawal, Kangyu Lin, Kanwal P.S. Raghav, Robert A. Wolff, Arvind Dasari, Ryan W. Huey, Bryan K. Kee, Michael J. Overman, Jason A. Willis, Phat H. Le, Michelle Escano, Yunyu C. Baig, Kelsey Pan, David Menter, Alda L. Tam, Scott Kopetz

{"title":"Phase 1/2 trial of encorafenib, cetuximab, and nivolumab in microsatellite stable BRAFV600E metastatic colorectal cancer","authors":"Van K. Morris, Christine M. Parseghian, Vahid Bahrambeigi, Nourhan Abdelfattah, Lianchun Xiao, Anjali Agrawal, Kangyu Lin, Kanwal P.S. Raghav, Robert A. Wolff, Arvind Dasari, Ryan W. Huey, Bryan K. Kee, Michael J. Overman, Jason A. Willis, Phat H. Le, Michelle Escano, Yunyu C. Baig, Kelsey Pan, David Menter, Alda L. Tam, Scott Kopetz","doi":"10.1016/j.ccell.2025.08.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.08.002","url":null,"abstract":"The BRAF inhibitor encorafenib and anti-epidermal growth factor receptor (EGFR) antibody cetuximab modestly improve survival for patients with microsatellite stable (MSS) BRAFV600E metastatic colorectal cancer (mCRC), characterized by higher immune activation than MSS BRAFwild-type colorectal cancer (CRC). In this phase 1/2 study (NCT04017650<svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>) of 26 participants with MSS BRAFV600E mCRC who received encorafenib, cetuximab, and anti-PD-1 antibody nivolumab, we report an overall response rate of 50% (95% confidence interval [CI] 29–71) and median progression-free survival of 7.4 months (95% CI, 5.6–9.6). Transcriptomic profiling of pretreatment biopsies and extracellular vesicle RNA (evRNA) isolated from plasma show enrichment of non-canonical mitogen-activated protein kinase (MAPK) signaling and immune activation signatures for responders. Complement pathway activation enriches in non-responder biopsies. On serial evRNA profiling, decreased MAPK signature and increased interferon gamma response signature associate with sustained treatment benefit. MSS BRAFV600E mCRC with baseline MAPK activation and immune activation signatures may benefit from the triple combination but not with complement pathway activation.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"29 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911220","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}

引用次数: 0

Safety and efficacy of a STAT3-targeted cyclic oligonucleotide: From murine models to a phase 1 clinical trial in pet cats with oral cancer stat3靶向环寡核苷酸的安全性和有效性：从小鼠模型到口腔癌宠物猫的1期临床试验

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-28 DOI: 10.1016/j.ccell.2025.07.015

Jennifer R. Grandis, Katherine A. Skorupski, Ning Cheng, Zhibin Cui, Hua Li, Liam C. Woerner, Jovanka Gencel-Augusto, Yan Zeng, Jamie V. Shiah, Neil E. Bhola, Malabika Sen, Kelly Blum, Mi-Ok Kim, Daniel York, Robert B. Rebhun, Hong Chang, Natalia F. Murad, Adam B. Olshen, Ellen E. Sparger, Daniel E. Johnson

{"title":"Safety and efficacy of a STAT3-targeted cyclic oligonucleotide: From murine models to a phase 1 clinical trial in pet cats with oral cancer","authors":"Jennifer R. Grandis, Katherine A. Skorupski, Ning Cheng, Zhibin Cui, Hua Li, Liam C. Woerner, Jovanka Gencel-Augusto, Yan Zeng, Jamie V. Shiah, Neil E. Bhola, Malabika Sen, Kelly Blum, Mi-Ok Kim, Daniel York, Robert B. Rebhun, Hong Chang, Natalia F. Murad, Adam B. Olshen, Ellen E. Sparger, Daniel E. Johnson","doi":"10.1016/j.ccell.2025.07.015","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.07.015","url":null,"abstract":"STAT3 is an oncogenic transcription factor that activates cancer cell signaling and induces an immunosuppressive immune environment, making it an attractive therapeutic target. Transcription factors are exceptionally challenging targets and there are no Food and Drug Administration-approved STAT3 inhibitors. We previously reported positive pharmacodynamics of a linear STAT3 decoy oligonucleotide administered intratumorally in a phase 0 trial in patients with head and neck cancer squamous cell carcinoma (HNSCC). Here, we describe the anti-tumor and immune effects of a systemically administered cyclic STAT3 decoy (CS3D) in immunocompetent HNSCC murine models and the safety and efficacy of CS3D in a clinical trial in pet cats with HNSCC. Responders in the clinical trial (35% disease control rate) showed significant differences in selected peripheral blood immune parameters as well as elevated PD-1 expression in the tumors compared with non-responders. These findings support a clinical trial of CS3D in HNSCC patients.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"120 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911218","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}

引用次数: 0

From gene lists to context drift 从基因列表到环境漂移

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-21 DOI: 10.1016/j.ccell.2025.07.025

Zhongyang Lin, Dvir Aran

引用次数: 0

Unraveling lymphoma-induced immune senescence 解开淋巴瘤引起的免疫衰老

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-21 DOI: 10.1016/j.ccell.2025.07.009

Patrizia Mondello, Stephen M. Ansell

引用次数: 0

Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency 全基因组CRISPR筛选鉴定增强CAR-NK细胞抗肿瘤效力的关键靶点

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-21 DOI: 10.1016/j.ccell.2025.07.021

Alexander Biederstädt, Rafet Basar, Jeong-Min Park, Nadima Uprety, Rejeena Shrestha, Francia Reyes Silva, Merve Dede, John Watts, Sunil Acharya, Donghai Xiong, Bin Liu, May Daher, Hind Rafei, Pinaki Banerjee, Ping Li, Sanjida Islam, Huihui Fan, Mayra Shanley, Jingling Jin, Bijender Kumar, Vernikka Woods, Paul Lin, Silvia Tiberti, Ana Karen Nunez Cortes, Xin Ru Jiang, Inci Biederstädt, Patrick Zhang, Ye Li, Seema Rawal, Enli Liu, Luis Muniz-Feliciano, Gary M. Deyter, Elizabeth J. Shpall, Natalie Wall Fowlkes, Ken Chen, Katayoun Rezvani

{"title":"Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency","authors":"Alexander Biederstädt, Rafet Basar, Jeong-Min Park, Nadima Uprety, Rejeena Shrestha, Francia Reyes Silva, Merve Dede, John Watts, Sunil Acharya, Donghai Xiong, Bin Liu, May Daher, Hind Rafei, Pinaki Banerjee, Ping Li, Sanjida Islam, Huihui Fan, Mayra Shanley, Jingling Jin, Bijender Kumar, Vernikka Woods, Paul Lin, Silvia Tiberti, Ana Karen Nunez Cortes, Xin Ru Jiang, Inci Biederstädt, Patrick Zhang, Ye Li, Seema Rawal, Enli Liu, Luis Muniz-Feliciano, Gary M. Deyter, Elizabeth J. Shpall, Natalie Wall Fowlkes, Ken Chen, Katayoun Rezvani","doi":"10.1016/j.ccell.2025.07.021","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.07.021","url":null,"abstract":"Adoptive cell therapy using engineered natural killer (NK) cells is a promising approach for cancer treatment, with targeted gene editing offering the potential to further enhance their therapeutic efficacy. However, the spectrum of actionable genetic targets to overcome tumor and microenvironment-mediated immunosuppression remains largely unexplored. We performed multiple genome-wide CRISPR screens in primary human NK cells and identified critical checkpoints regulating resistance to immunosuppressive pressures. Ablation of <ce:italic>MED12</ce:italic>, <ce:italic>ARIH2</ce:italic>, and <ce:italic>CCNC</ce:italic> significantly improved NK cell antitumor activity against multiple treatment-refractory human cancers <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic>. CRISPR editing augmented both innate and CAR-mediated NK cell function, associated with enhanced metabolic fitness, increased secretion of proinflammatory cytokines, and expansion of cytotoxic NK cell subsets. Through high-content genome-wide CRISPR screening in NK cells, this study reveals critical regulators of NK cell function and provides a valuable resource for engineering next-generation NK cell therapies with improved efficacy against cancer.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"22 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900564","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}

引用次数: 0