Cancer Cell最新文献

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Pan-cancer human brain metastases atlas at single-cell resolution 单细胞分辨率的泛癌人脑转移图谱
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.025
Xudong Xing, Jian Zhong, Jana Biermann, Hao Duan, Xinyu Zhang, Yu Shi, Yixin Gao, Kejun He, Duanyang Zhai, Feng Luo, Yanxing Lai, Feizhe Xiao, Wenying Wang, Mengru Wang, Jianguo Xu, Hao Liu, Jiaze Tang, Liangzhao Chu, Tunan Chen, Edridge K. D’Souza, Fan Bai
{"title":"Pan-cancer human brain metastases atlas at single-cell resolution","authors":"Xudong Xing, Jian Zhong, Jana Biermann, Hao Duan, Xinyu Zhang, Yu Shi, Yixin Gao, Kejun He, Duanyang Zhai, Feng Luo, Yanxing Lai, Feizhe Xiao, Wenying Wang, Mengru Wang, Jianguo Xu, Hao Liu, Jiaze Tang, Liangzhao Chu, Tunan Chen, Edridge K. D’Souza, Fan Bai","doi":"10.1016/j.ccell.2025.03.025","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.025","url":null,"abstract":"Brain metastases (BrMs) remain a major clinical and therapeutic challenge in patients with metastatic cancers. However, advances in our understanding of BrM have been hampered by the constrained sample size and resolution of BrM profiling studies. Here, we perform integrative single-cell RNA sequencing analysis on 108 BrM samples and 111 primary tumor (PTs) samples to investigate the characteristics and remodeling of cell states and composition across cancer lineages and subsets. Recurring and enriched features of malignant cells are increased chromosomal instability, marked proliferative and angiogenic hallmarks, and adoption of a neural-like BrM-associated metaprogram. Immunosuppressive myeloid and stromal subsets dominate the BrM tumor microenvironment, which are associated with poor prognosis and resistance to immunotherapy. Furthermore, five distinct BrM ecotypes are identified, correlating with specific histopathological patterns and clinical characteristics. This work defines hallmarks of BrM biology across cancer types and suggests that shared dependencies may exist, which may be exploited clinically.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"89 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814006","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
Radiotherapy promotes cuproptosis and synergizes with cuproptosis inducers to overcome tumor radioresistance 放疗促进铜体增生,并与铜体增生诱导剂协同克服肿瘤放射耐药
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.031
Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Boyi Gan
{"title":"Radiotherapy promotes cuproptosis and synergizes with cuproptosis inducers to overcome tumor radioresistance","authors":"Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Boyi Gan","doi":"10.1016/j.ccell.2025.03.031","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.031","url":null,"abstract":"Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins—both hallmarks of cuproptosis—in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the expression of copper-sequestering metallothionein (MT) 1E/X, thereby mitigating cuproptosis and contributing to radioresistance. Copper ionophore treatment sensitizes radioresistant cancer cells and cell line- and patient-derived xenografts to RT by potentiating cuproptosis. Our findings unveil a link between RT and cuproptosis and inform a therapeutic strategy to overcome tumor radioresistance by targeting cuproptosis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"107 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814001","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
Spatial determinants of antibody-drug conjugate SHR-A1811 efficacy in neoadjuvant treatment for HER2-positive breast cancer SHR-A1811抗体-药物偶联物在her2阳性乳腺癌新辅助治疗中疗效的空间决定因素
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.017
Ding Ma, Lei-Jie Dai, Xiang-Rong Wu, Cheng-Lin Liu, Shen Zhao, Hang Zhang, Li Chen, Yi Xiao, Ming Li, Yi-Zhi Zhao, Lin Yang, Tong Zhou, Jun-Jie Li, Wen-Tao Yang, Yi-Zhou Jiang, Zhi-Ming Shao
{"title":"Spatial determinants of antibody-drug conjugate SHR-A1811 efficacy in neoadjuvant treatment for HER2-positive breast cancer","authors":"Ding Ma, Lei-Jie Dai, Xiang-Rong Wu, Cheng-Lin Liu, Shen Zhao, Hang Zhang, Li Chen, Yi Xiao, Ming Li, Yi-Zhi Zhao, Lin Yang, Tong Zhou, Jun-Jie Li, Wen-Tao Yang, Yi-Zhou Jiang, Zhi-Ming Shao","doi":"10.1016/j.ccell.2025.03.017","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.017","url":null,"abstract":"Selecting optimal candidates for next-generation anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) remains challenging. We conduct a prespecified translational study to identify treatment biomarkers in SHR-A1811-treated HER2-positive breast cancer patients from the phase 2 neoadjuvant FASCINATE-N trial using DNA and RNA sequencing, computational pathology, and single-cell <em>in situ</em> spatial imaging. In the hormone receptor (HR)-negative subgroup, a higher proportion and more infiltration of immune cells (i.e., tumor-infiltrating lymphocytes [TILs]), particularly cytotoxic T cells, are associated with better treatment responses. In the HR-positive subgroup, the closeness and aggregation of HER2-strong-positive tumor cells, as opposed to a uniform distribution, are linked to a lower response rate and HER2 luminal-like (HER2-LUM) subtype, which more closely resembles HR+/HER2− breast cancer. In addition, we develop a clinically practical predictive model capable of predicting neoadjuvant treatment responses to SHR-A1811 and other novel ADCs based on clinicopathological characteristics and pathological images.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"3 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814002","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
Neoadjuvant toripalimab plus nimotuzumab combined with taxol-based chemotherapy in locally advanced penile squamous cell carcinoma 局部晚期阴茎鳞状细胞癌的新辅助托利帕利单抗加尼莫妥珠单抗联合紫杉醇化疗
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.023
Xin An, Sheng Jie Guo, Ru Yan, Ting Xue, Long Bin Xiong, Hua Li Ma, Cong Xue, Ying Chun Zhang, Ji Bin Li, Mei Ting Chen, Zai Shang Li, Ting Yu Liu, Zhi Ling Zhang, Pei Dong, Yong Hong Li, Kai Yao, Zhi Quan Hu, Xiao Feng Chen, Jie Xin Luo, Yong Hong Lei, Hui Han
{"title":"Neoadjuvant toripalimab plus nimotuzumab combined with taxol-based chemotherapy in locally advanced penile squamous cell carcinoma","authors":"Xin An, Sheng Jie Guo, Ru Yan, Ting Xue, Long Bin Xiong, Hua Li Ma, Cong Xue, Ying Chun Zhang, Ji Bin Li, Mei Ting Chen, Zai Shang Li, Ting Yu Liu, Zhi Ling Zhang, Pei Dong, Yong Hong Li, Kai Yao, Zhi Quan Hu, Xiao Feng Chen, Jie Xin Luo, Yong Hong Lei, Hui Han","doi":"10.1016/j.ccell.2025.03.023","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.023","url":null,"abstract":"The conventional neoadjuvant chemotherapy regimen for locally advanced penile squamous cell carcinoma (La-PSCC) has shown moderate response rates and survival benefits. This single-arm, phase II trial (<span><span>NCT04475016</span><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></span>) evaluated a neoadjuvant regimen of four cycles of toripalimab (anti-PD-1 antibody), nimotuzumab (anti-EGFR antibody), and taxol-based chemotherapy (TNT), followed by consolidative surgery. The primary endpoint was the pathological complete response (pCR) rate. Among 29 enrolled patients, 24 (82.8%) underwent consolidative surgery, with 14 (48.3%, 95% confidence interval [CI], 29.4–67.5%) achieving pCR. The objective response rate (ORR) was 82.8% (95% CI, 64.2–94.2). Median follow-up was 39.97 months, with two-year overall survival (OS) and progression-free survival (PFS) rates of 72.4% and 65.5%. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 12 (41.4%) patients, with no treatment-related deaths. Biomarker analysis identified PD-L1 expression, TP53 mutation status, and CD8<sup>+</sup> T cell density as potential predictive markers. Therefore, neoadjuvant TNT shows promising anti-tumor activity and acceptable toxicity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"60 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814004","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
ZEB2 is a master switch controlling the tumor-associated macrophage program ZEB2是控制肿瘤相关巨噬细胞程序的主开关
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.021
Fadi Sheban, Truong San Phan, Ken Xie, Florian Ingelfinger, Chamutal Gur, Yuval Shapir Itai, Ronnie Blecher-Gonen, Chunsong Yu, Roberto Avellino, Paulina Chalan, Kiara Freitag, Ido Yofe, Vladimir Yutkin, Pierre Boyeau, Can Ergen, Justin Hong, Kfir Mazuz, Yuxiao Liu, Kangming Chen, Rony Dahan, Ido Amit
{"title":"ZEB2 is a master switch controlling the tumor-associated macrophage program","authors":"Fadi Sheban, Truong San Phan, Ken Xie, Florian Ingelfinger, Chamutal Gur, Yuval Shapir Itai, Ronnie Blecher-Gonen, Chunsong Yu, Roberto Avellino, Paulina Chalan, Kiara Freitag, Ido Yofe, Vladimir Yutkin, Pierre Boyeau, Can Ergen, Justin Hong, Kfir Mazuz, Yuxiao Liu, Kangming Chen, Rony Dahan, Ido Amit","doi":"10.1016/j.ccell.2025.03.021","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.021","url":null,"abstract":"Tumor-associated macrophages (TAMs) are key mediators of tumor immune evasion. However, their regulatory circuits and checkpoints are partially understood. Here, we generated a TAM regulatory network by integrating human tumors single-cell RNA sequencing (scRNA-seq) data with a dedicated CRISPR screen. Using a deep generative model, we constructed a gene perturbation network linking individual candidates with prototypical TAM functions. We identified <em>Zeb2</em> as the master regulator of TAM programs, orchestrating suppression of type-I interferon response and antigen presentation alongside activation of immune suppression programs. Genetic ablation of ZEB2 reprograms TAM function and identity on the chromatin, RNA, and protein levels. In macrophage-rich human tumors, <em>ZEB2</em> expression is associated with poor prognosis. Selective <em>Zeb2 in vivo</em> targeting reprograms TAMs and mobilizes systemic T cell responses, achieving robust tumor clearance. Overall, our study generates a detailed roadmap of TAM gene circuits and identifies <em>ZEB2</em> as a master switch with therapeutic potential.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"183 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814007","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
AI-driven biomarkers for antibody-drug conjugates 人工智能驱动的抗体-药物偶联物生物标志物
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.020
Sherene Loi, Roberto Salgado
{"title":"AI-driven biomarkers for antibody-drug conjugates","authors":"Sherene Loi, Roberto Salgado","doi":"10.1016/j.ccell.2025.03.020","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.020","url":null,"abstract":"Currently, no biomarker reliably predicts the efficacy of antibody-drug conjugates (ADCs). In this issue of <em>Cancer Cell</em>, Ma et al. present a predictive model for HER2-targeting ADC efficacy, incorporating immune-system components, hormone receptor status, clinical staging, and HER2+ cell proportion.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"25 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814005","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
Diet-microbiome interactions in cancer 饮食-微生物组在癌症中的相互作用
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-03 DOI: 10.1016/j.ccell.2025.03.013
Suhaib K. Abdeen, Ignacio Mastandrea, Nina Stinchcombe, Jens Puschhof, Eran Elinav
{"title":"Diet-microbiome interactions in cancer","authors":"Suhaib K. Abdeen, Ignacio Mastandrea, Nina Stinchcombe, Jens Puschhof, Eran Elinav","doi":"10.1016/j.ccell.2025.03.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.013","url":null,"abstract":"Diet impacts cancer in diverse manners. Multiple nutritional effects on tumors are mediated by dietary modulation of commensals, residing in mucosal surfaces and possibly also within the tumor microenvironment. Mechanistically understanding such diet-microbiome-host interactions may enable to develop precision nutritional interventions impacting cancer development, dissemination, and treatment responses. However, data-driven nutritional strategies integrating diet-microbiome interactions are infrequently incorporated into cancer prevention and treatment schemes. Herein, we discuss how dietary composition affects cancer-related processes through alterations exerted by specific nutrients and complex foods on the microbiome. We highlight how dietary timing, including time-restricted feeding, impacts microbial function in modulating cancer and its therapy. We review existing and experimental nutritional approaches aimed at enhancing microbiome-mediated cancer treatment responsiveness while minimizing adverse effects, and address challenges and prospects in integrating diet-microbiome interactions into precision oncology. Collectively, mechanistically understanding diet-microbiome-host interactomes may enable to achieve a personalized and microbiome-informed optimization of nutritional cancer interventions.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"16 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766916","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
Spatial transcriptomics reveals tryptophan metabolism restricting maturation of intratumoral tertiary lymphoid structures 空间转录组学揭示了色氨酸代谢限制肿瘤内三级淋巴样结构的成熟
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-03 DOI: 10.1016/j.ccell.2025.03.011
Zhonghui Tang, Yinqi Bai, Qi Fang, Yuchen Yuan, Qianwen Zeng, Shuling Chen, Tianyi Xu, Jianyu Chen, Li Tan, Chunqing Wang, Qian Li, Jinpei Lin, Zhuoxuan Yang, Xia Wu, Guowei Shi, Ji Wang, Changjun Yin, Jianping Guo, Shiping Liu, Sui Peng, Ming Kuang
{"title":"Spatial transcriptomics reveals tryptophan metabolism restricting maturation of intratumoral tertiary lymphoid structures","authors":"Zhonghui Tang, Yinqi Bai, Qi Fang, Yuchen Yuan, Qianwen Zeng, Shuling Chen, Tianyi Xu, Jianyu Chen, Li Tan, Chunqing Wang, Qian Li, Jinpei Lin, Zhuoxuan Yang, Xia Wu, Guowei Shi, Ji Wang, Changjun Yin, Jianping Guo, Shiping Liu, Sui Peng, Ming Kuang","doi":"10.1016/j.ccell.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.011","url":null,"abstract":"Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates found in numerous cancers, often linked to enhanced immunotherapy responses and better clinical outcomes. However, the factors driving TLS maturation are not fully understood. Using near single-cell spatial transcriptomic mapping, we comprehensively profile TLSs under various maturation stages and their microenvironment in hepatocellular carcinoma (HCC). Based on their developmental trajectories, we classify immature TLSs into two groups: conforming and deviating TLSs. Our findings indicate that conforming TLSs, similar to mature TLSs, possess a niche function for immunotherapy responses, while deviating TLSs do not. We discover that the tryptophan-enriched metabolic microenvironment shaped by malignant cells contributes to the deviation of TLS maturation. Inhibiting tryptophan metabolism promotes intratumoral TLS maturation and enhances tumor control, synergizing with anti-PD-1 treatments. Therefore, promoting TLS maturation represents a potential strategy to improve antitumor responses and immunotherapy outcomes.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"10 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766921","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
Proteogenomic characterization of non-functional pancreatic neuroendocrine tumors unravels clinically relevant subgroups 非功能性胰腺神经内分泌肿瘤的蛋白质基因组学特征揭示了临床相关亚群
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-03 DOI: 10.1016/j.ccell.2025.03.016
Shunrong Ji, Lihua Cao, Jing Gao, Yang Du, Zeng Ye, Xin Lou, Fen Liu, Yehan Zhang, Junfeng Xu, Xiaohan Shi, Huan Wang, Penghao Li, Yikai Li, Hongxu Chen, Zhicheng Yang, Suizhi Gao, Wuhu Zhang, Dan Huang, Shujuan Ni, Miaoyan Wei, Xianjun Yu
{"title":"Proteogenomic characterization of non-functional pancreatic neuroendocrine tumors unravels clinically relevant subgroups","authors":"Shunrong Ji, Lihua Cao, Jing Gao, Yang Du, Zeng Ye, Xin Lou, Fen Liu, Yehan Zhang, Junfeng Xu, Xiaohan Shi, Huan Wang, Penghao Li, Yikai Li, Hongxu Chen, Zhicheng Yang, Suizhi Gao, Wuhu Zhang, Dan Huang, Shujuan Ni, Miaoyan Wei, Xianjun Yu","doi":"10.1016/j.ccell.2025.03.016","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.016","url":null,"abstract":"The majority of neuroendocrine neoplasms in pancreas are non-functional pancreatic neuroendocrine tumors (NF-PanNETs), which exhibit a high occurrence of distant metastases with limited therapeutic options. Here, we perform a comprehensive molecular characterization of 108 NF-PanNETs through integrative analysis of genomic, transcriptomic, proteomic, and phosphoproteomic profiles. Proteogenomic analysis provides functional insights into the genomic driver alterations of NF-PanNETs, revealing a potential mediator of <em>MEN1</em> alterations using <em>Men1</em>-conditional knockout mice. Machine-learning-based modeling uncovers a three-protein signature as an independent prognostic factor, which is validated by an independent external cohort. Proteomic and phosphoproteomic-based stratification identifies four subtypes with distinct molecular characteristics, immune microenvironments, and clinicopathological features. Drug screening using patient-derived tumor organoids identifies cyclin-dependent kinase (CDK) 5 and Calcium Voltage-Gated Channel Subunit Alpha1 D (CACNA1D) as ubiquitous and subtype-specific targets, respectively, with <em>in vivo</em> validation using xenograft models. Together, our proteogenomic analyses illustrate a comprehensive molecular landscape of NF-PanNETs, revealing biological insights and therapeutic vulnerabilities.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"133 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766926","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 Terry Fox Research Institute Marathon of Hope Cancer Centres Network: A pan-Canadian precision oncology initiative 泰瑞福克斯研究所马拉松希望癌症中心网络:一个泛加拿大精确肿瘤学倡议
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-03 DOI: 10.1016/j.ccell.2025.03.014
{"title":"The Terry Fox Research Institute Marathon of Hope Cancer Centres Network: A pan-Canadian precision oncology initiative","authors":"","doi":"10.1016/j.ccell.2025.03.014","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.014","url":null,"abstract":"The Marathon of Hope Cancer Centres Network (<span><span>MOHCCN</span><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></span>), led by the Terry Fox Research Institute and the Terry Fox Foundation, unites researchers, clinicians, patients, funders, and other partners across Canada to accelerate precision oncology, promote collaboration and data sharing, and ultimately improve patient outcomes. This overview outlines the Network’s goals, history, and challenges and opportunities. We also highlight progress toward the “MOHCCN Gold Cohort,” a shared resource of clinical and genomic data from 15,000 patients.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"37 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766839","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
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