Cancer Cell最新文献_第3页

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

Lymphoma accelerates T cell and tissue aging 淋巴瘤加速T细胞和组织老化

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-21 DOI: 10.1016/j.ccell.2025.07.023

Rebecca S. Hesterberg, Joshua T. Davis, Komal J. Handoo, Aya G. Elmarsafawi, Anthony C. Augello, Chia-Ho Cheng, Reginald Atkins, Dae Hyun Lee, Chunying Yang, Jiqiang Yao, Krishna R. Patel, Melanie Mediavilla-Varela, Javier Pinilla-Ibarz, Carolina Soto-Palma, Frederick L. Locke, Xiaofei Song, Xuefeng Wang, Anders E. Berglund, Paulo C. Rodriguez, Gero Knittel, Ruth Flümann, Hans Christian Reinhardt, Timothy I. Shaw, Xiaoqing Yu, Laura J. Niedernhofer, John L. Cleveland

{"title":"Lymphoma accelerates T cell and tissue aging","authors":"Rebecca S. Hesterberg, Joshua T. Davis, Komal J. Handoo, Aya G. Elmarsafawi, Anthony C. Augello, Chia-Ho Cheng, Reginald Atkins, Dae Hyun Lee, Chunying Yang, Jiqiang Yao, Krishna R. Patel, Melanie Mediavilla-Varela, Javier Pinilla-Ibarz, Carolina Soto-Palma, Frederick L. Locke, Xiaofei Song, Xuefeng Wang, Anders E. Berglund, Paulo C. Rodriguez, Gero Knittel, Ruth Flümann, Hans Christian Reinhardt, Timothy I. Shaw, Xiaoqing Yu, Laura J. Niedernhofer, John L. Cleveland","doi":"10.1016/j.ccell.2025.07.023","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.07.023","url":null,"abstract":"The combined effects of aging and cancer on immune cells were investigated in young versus aged mice harboring B cell lymphoma, and in T cells from young and aged B cell lymphoma patients. These analyses revealed that lymphoma alone is sufficient to trigger transcriptional, epigenetic, and phenotypic alterations in young T cells that manifest in aged T cells. In contrast, aged T cells are largely resistant to lymphoma-induced changes. Pathway analyses revealed open chromatin regions and genes controlling iron homeostasis are induced by both lymphoma and aging, and lymphoma-experienced and aged T cells have increased iron pools and are resistant to ferroptosis. Furthermore, both aged and lymphoma-experienced T cells have defects in proteostasis. B cell lymphoma also accelerates aging of other tissues, as evidenced by elevated expression of <ce:italic>Cdkn2a</ce:italic> and <ce:italic>Tnfa</ce:italic>. Finally, some lymphoma-induced aging phenotypes are reversible whereas others are fixed, indicating opportunities for improving some cancer-associated aging comorbidities.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"185 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900565","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

DNASE1L3-expressing dendritic cells promote CD8+ T cell function and anti-PD-(L)1 therapy efficacy by degrading neutrophil extracellular traps 表达dnase1l3的树突状细胞通过降解中性粒细胞胞外陷阱促进CD8+ T细胞功能和抗pd -(L)1治疗效果

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-14 DOI: 10.1016/j.ccell.2025.07.014

Degao Chen, Zheng Jin, Han Chu, Yucui Wu, Yangping Bian, Ting Yuan, Hao Lv, Qiuyu Xia, Lei Wang, Qian Chu, Quanxing Liu, Dong Zhou, Wenfeng Fang, Xiaoming Cheng, Haoran Zha, Haixia Long, Li Zhang, Jigang Dai, Yisong Y. Wan, Qi-Jing Li, Bo Zhu

{"title":"DNASE1L3-expressing dendritic cells promote CD8+ T cell function and anti-PD-(L)1 therapy efficacy by degrading neutrophil extracellular traps","authors":"Degao Chen, Zheng Jin, Han Chu, Yucui Wu, Yangping Bian, Ting Yuan, Hao Lv, Qiuyu Xia, Lei Wang, Qian Chu, Quanxing Liu, Dong Zhou, Wenfeng Fang, Xiaoming Cheng, Haoran Zha, Haixia Long, Li Zhang, Jigang Dai, Yisong Y. Wan, Qi-Jing Li, Bo Zhu","doi":"10.1016/j.ccell.2025.07.014","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.07.014","url":null,"abstract":"CD8+ T cell exclusion and dysfunction in the tumor microenvironment (TME) are among the most challenging obstacles for anti-PD-(L)1 therapy. Here, we report that tumor-infiltrating dendritic cell (DC)-specific expression of the deoxyribonuclease, DNASE1L3, is positively correlated with favorable outcomes of anti-PD-(L)1 treatment in cancer patients. DNASE1L3 conditional knockout in DCs leads to enhanced tumor growth and diminishes anti-PD-L1 therapeutic efficacy by impairing infiltration and effector functions of CD8+ T cells. Conversely, injection with DNASE1L3 promotes CD8+ T cell infiltration and reduces exhaustion in the TME, significantly retarding tumor growth and enhancing anti-PD-L1 response. DNASE1L3+ DCs can degrade neutrophil extracellular traps that suppress the spatial distribution of CD8+ T cells in tumors, enabling establishment of cytotoxic CD8+ T cell hubs in human cancers. Our findings reveal a role of DC in regulating intratumoral CD8+ T cells and identify DNASE1L3 as a promising target to improve anti-PD-(L)1 therapy.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"22 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840304","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

Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer fc优化的CD40激动抗体在转移性肿瘤中诱导三级淋巴样结构的形成和全身抗肿瘤免疫

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-14 DOI: 10.1016/j.ccell.2025.07.013

Juan C. Osorio, David A. Knorr, Polina Weitzenfeld, Lucas Blanchard, Ning Yao, Maria Baez, Carlo Sevilla, Meghan DiLillo, Jahan Rahman, Ved P. Sharma, Jacqueline Bromberg, Michael A. Postow, Charlotte Ariyan, Mark E. Robson, Jeffrey V. Ravetch

{"title":"Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer","authors":"Juan C. Osorio, David A. Knorr, Polina Weitzenfeld, Lucas Blanchard, Ning Yao, Maria Baez, Carlo Sevilla, Meghan DiLillo, Jahan Rahman, Ved P. Sharma, Jacqueline Bromberg, Michael A. Postow, Charlotte Ariyan, Mark E. Robson, Jeffrey V. Ravetch","doi":"10.1016/j.ccell.2025.07.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.07.013","url":null,"abstract":"CD40 agonism enhances antitumor immunity but is limited by systemic toxicity and poor efficacy. Here, we present a phase 1 study (NCT04059588<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 intratumoral (i.t.) 2141-V11, an Fc-engineered anti-CD40 agonistic antibody with enhanced binding to the inhibitory receptor FcγRIIB. Among 12 metastatic cancer patients, 2141-V11 was well tolerated without dose-limiting toxicities. Six patients experienced tumor reduction, including two complete responses in melanoma and breast cancer. 2141-V11 induced regression in injected and non-injected lesions, correlating with systemic CD8+ T cell activation and mature tertiary lymphoid structures (TLSs) in complete responders. In CD40/FcγRs humanized mice bearing orthotopic tumors, i.t. 2141-V11 promoted de novo TLS formation, facilitating i.t. CD8+ T cell effector responses independent of lymph node priming. The resulting local immune responses by 2141-V11 mediated abscopal antitumor effects and sustained immune memory. These findings demonstrate that i.t. 2141-V11 is safe and promotes immune-privileged tumor microenvironments that promote systemic and durable antitumor immunity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"9 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840305","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

Dendritic cells function beyond antigen presentation 树突状细胞的功能超越抗原呈递

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-08-14 DOI: 10.1016/j.ccell.2025.07.003

Eynav Klechevsky

引用次数: 0

Long-range cholinergic input promotes glioblastoma progression. 远距离胆碱能输入促进胶质母细胞瘤的进展。

IF 44.5 1区医学

Cancer Cell Pub Date : 2025-08-12 DOI: 10.1016/j.ccell.2025.07.024

Yang Yang, Chuanyan Yang, Xuezhu Chen, Yibin Jiang, Xuejiao Lei, Kang Ma, Yulian Quan, Tianran Li, Chenfu Guo, Yijing Meng, Lin Kang, Xinyu Zhang, Long Jin, Jiafeng Huang, Ning Mu, Zexuan Yan, Qinghua Ma, Shuai Wang, Yanxia Wang, Yong-Ning Shang, Cong Chen, Yu Shi, Shukun Hu, Likun Yang, Chuan Lan, Rong Hu, Ying Zhang, Xia Li, Yunqing Li, Chong Liu, Yu-Hai Wang, Fei Li, Hua Feng, Xiu-Wu Bian, Tunan Chen

{"title":"Long-range cholinergic input promotes glioblastoma progression.","authors":"Yang Yang, Chuanyan Yang, Xuezhu Chen, Yibin Jiang, Xuejiao Lei, Kang Ma, Yulian Quan, Tianran Li, Chenfu Guo, Yijing Meng, Lin Kang, Xinyu Zhang, Long Jin, Jiafeng Huang, Ning Mu, Zexuan Yan, Qinghua Ma, Shuai Wang, Yanxia Wang, Yong-Ning Shang, Cong Chen, Yu Shi, Shukun Hu, Likun Yang, Chuan Lan, Rong Hu, Ying Zhang, Xia Li, Yunqing Li, Chong Liu, Yu-Hai Wang, Fei Li, Hua Feng, Xiu-Wu Bian, Tunan Chen","doi":"10.1016/j.ccell.2025.07.024","DOIUrl":"10.1016/j.ccell.2025.07.024","url":null,"abstract":"Glioblastoma (GBM), the most aggressive primary brain tumor, is shaped by its integration into neural networks. While glutamatergic input is linked to tumor progression, the broader architecture and function of neuron-glioma connectomes remain unclear. Using monosynaptic rabies tracing, we map brain-wide neural input to patient-derived xenografts and reveal a consistent organizational logic: local inputs are primarily glutamatergic, while long-range connections exhibit diverse neurotransmitter profiles, with basal forebrain cholinergic projections emerging as a conserved input across sites. Functionally, presynaptic acetylcholine release promotes GBM progression through muscarinic receptor CHRM3 in a circuit-specific manner. Mechanistically, glutamatergic and cholinergic signals converge to enhance glioma calcium transients but diverge in temporal transcriptional control, with their dual blockade producing additive anti-tumor effects. Therapeutically, the anticholinergic drug scopolamine attenuates glioma growth, whereas the acetylcholinesterase inhibitor donepezil exacerbates disease. These findings reveal the complexity of neuron-glioma connectivity, highlighting long-range neuromodulatory pathways as promising therapeutic targets in GBM.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882291","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