Cancer Cell最新文献

TAMing immunity through an unexpected source 通过一个意想不到的来源驯服免疫

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-01 DOI: 10.1016/j.ccell.2025.04.004

Ian Vogel, Sagar P. Bapat

引用次数: 0

Ribosomal rebellion: When protein factories drive cancer progression 核糖体叛乱：当蛋白质工厂驱动癌症进展

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.03.035

Qiushuang Wu, Sohail F. Tavazoie

引用次数: 0

Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts 骨转移瘤通过产生骨桥蛋白的破骨细胞减少对检查点阻断免疫疗法的骨外反应

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.03.036

Jia-Nan Cheng, Zheng Jin, Chunxia Su, Tao Jiang, Xiaobin Zheng, Jinming Guo, Xingyi Li, Han Chu, Jia Jia, Qin Zhou, Xiaofang Ding, Yiwen Zhang, Shouxia Xu, Fancong Dong, Qiao Zhang, Xinxin Yang, Tao Yang, Xiaoming Cheng, Haoran Zha, Degao Chen, Bo Zhu

{"title":"Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts","authors":"Jia-Nan Cheng, Zheng Jin, Chunxia Su, Tao Jiang, Xiaobin Zheng, Jinming Guo, Xingyi Li, Han Chu, Jia Jia, Qin Zhou, Xiaofang Ding, Yiwen Zhang, Shouxia Xu, Fancong Dong, Qiao Zhang, Xinxin Yang, Tao Yang, Xiaoming Cheng, Haoran Zha, Degao Chen, Bo Zhu","doi":"10.1016/j.ccell.2025.03.036","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.036","url":null,"abstract":"Bone metastatic lesions typically associate with suboptimal responses to immune checkpoint blockade (ICB) therapies. In this study, we observed that across multiple clinical cohorts and a variety of mouse models, the presence of osseous metastases induces ICB resistance in extraosseous tumors. Mechanistically, this long-distance communication is mediated by osseous tumor-conditioned osteoclasts producing osteopontin (OPN). Through circulation, OPN reprograms the extraosseous tumor microenvironment and impairs T cell recruitment and differentiation of CD8+TCF1+ precursor cells, an essential population for ICB efficacy. In mice, ICB responsiveness is restored by αRANKL blockade of osteoclastogenesis, neutralization of OPN in circulation, or tissue-specific depletion of OPN in osteoclasts. Both the mode of action and therapeutic benefit were validated in clinical cohorts with the αRANKL-ICB combinatory regimen. These findings establish bone as a specific immunoregulatory organ exploited by tumor metastasis and suggest osteoclastogenesis as a promising target to improve ICB prognosis in patients with bone metastasis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"32 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866995","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

Easing cisplatin’s toll in nasopharyngeal carcinoma 缓解顺铂在鼻咽癌中的作用

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.03.034

Michael J. Dennis, Ravindra Uppaluri

引用次数: 0

Stromal lipid species dictate melanoma metastasis and tropism 基质脂质种类决定黑色素瘤的转移和趋向性

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.04.001

Shilpa Gurung, Timothy Budden, Karthik Mallela, Benjamin Jenkins, Alex von Kriegsheim, Esperanza Manrique, David Millán-Esteban, Isabel Romero-Camarero, Fabio Amaral, Sarah Craig, Pedro Durao, Joanna Pozniak, Laura Stennett, Duncan Smith, Garry Ashton, Alex Baker, Kang Zeng, Gilbert Fruhwirth, Victoria Sanz-Moreno, Jair Marques, Amaya Virós

{"title":"Stromal lipid species dictate melanoma metastasis and tropism","authors":"Shilpa Gurung, Timothy Budden, Karthik Mallela, Benjamin Jenkins, Alex von Kriegsheim, Esperanza Manrique, David Millán-Esteban, Isabel Romero-Camarero, Fabio Amaral, Sarah Craig, Pedro Durao, Joanna Pozniak, Laura Stennett, Duncan Smith, Garry Ashton, Alex Baker, Kang Zeng, Gilbert Fruhwirth, Victoria Sanz-Moreno, Jair Marques, Amaya Virós","doi":"10.1016/j.ccell.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.001","url":null,"abstract":"Cancer cells adapt to signals in the tumor microenvironment (TME), but the TME cues that impact metastasis and tropism are still incompletely understood. We show that abundant stromal lipids from young subcutaneous adipocytes, including phosphatidylcholines, are taken up by melanoma cells, where they upregulate melanoma PI3K-AKT signaling, fatty acid oxidation, oxidative phosphorylation (OXPHOS) leading to oxidative stress, resulting in decreased metastatic burden. High OXPHOS melanoma cells predominantly seed the lung and brain; decreasing oxidative stress with antioxidants shifts tropism from the lung to the liver. By contrast, the aged TME provides fewer total lipids but is rich in ceramides, leading to lower OXPHOS and high metastatic burden. Aged TME ceramides taken up by melanoma cells activate the S1P-STAT3-IL-6 signaling axis and promote liver tropism. Inhibiting OXPHOS in the young TME or blocking the IL-6 receptor in the aged TME reduces the age-specific patterns of metastasis imposed by lipid availability.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"14 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866997","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

KMT2C deficiency drives transdifferentiation of double-negative prostate cancer and confer resistance to AR-targeted therapy KMT2C缺陷驱动双阴性前列腺癌转分化并赋予对ar靶向治疗的抗性

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.04.002

Jiacheng Guo, Ni Li, Qiuli Liu, Zongyao Hao, Guanghui Zhu, Xuege Wang, Hanling Wang, Qiang Pan, Beitao Xu, Ying Han, Guoying Zhang, Yannan Lian, Wei Zhang, Yongqiang Gu, Naiheng Lin, Xin Zeng, Zige Jin, Weihua Lan, Jun Jiang, Dong Gao, Jun Qin

{"title":"KMT2C deficiency drives transdifferentiation of double-negative prostate cancer and confer resistance to AR-targeted therapy","authors":"Jiacheng Guo, Ni Li, Qiuli Liu, Zongyao Hao, Guanghui Zhu, Xuege Wang, Hanling Wang, Qiang Pan, Beitao Xu, Ying Han, Guoying Zhang, Yannan Lian, Wei Zhang, Yongqiang Gu, Naiheng Lin, Xin Zeng, Zige Jin, Weihua Lan, Jun Jiang, Dong Gao, Jun Qin","doi":"10.1016/j.ccell.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.002","url":null,"abstract":"Double-negative prostate cancer (DNPC), characterized by an androgen receptor (AR)- and neuroendocrine-null phenotype, frequently emerges following androgen deprivation therapy (ADT). However, our understanding of the origins and regulatory mechanisms of DNPC remains limited. Here, we discover that tumors with KMT2C mutation or loss are highly susceptible to transitioning into DNPC following ADT. We clarify that DNPC primarily stems from luminal cell transdifferentiation rather than basal cell transformation. Antiandrogen treatment induces KMT2C binding at enhancers of a subset of AR-regulated genes, preserving the adenocarcinoma lineage. KMT2C maintains ASPP2 expression via enhancer-promoter communication post-AR inhibition, while its inactivation reduces ASPP2, triggering ΔNp63-dependent transdifferentiation. This DNPC transition maintains fatty acid (FA) synthesis through ΔNp63-mediated SREBP1c transactivation, fueling DNPC growth via HRAS palmitoylation and MAPK signaling activation. These findings highlight KMT2C as an epigenetic checkpoint against DNPC development and suggest the therapeutic potential of targeting fatty acid synthesis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"7 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866998","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 predictive biomarker discovery with contrastive learning to improve clinical trial outcomes 人工智能驱动的预测性生物标志物发现与对比学习，以改善临床试验结果

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.029

Gustavo Arango-Argoty, Damian E. Bikiel, Gerald J. Sun, Elly Kipkogei, Kaitlin M. Smith, Sebastian Carrasco Pro, Elizabeth Y. Choe, Etai Jacob

{"title":"AI-driven predictive biomarker discovery with contrastive learning to improve clinical trial outcomes","authors":"Gustavo Arango-Argoty, Damian E. Bikiel, Gerald J. Sun, Elly Kipkogei, Kaitlin M. Smith, Sebastian Carrasco Pro, Elizabeth Y. Choe, Etai Jacob","doi":"10.1016/j.ccell.2025.03.029","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.029","url":null,"abstract":"Modern clinical trials can capture tens of thousands of clinicogenomic measurements per individual. Discovering predictive biomarkers, as opposed to prognostic markers, remains challenging. To address this, we present a neural network framework based on contrastive learning—the Predictive Biomarker Modeling Framework (PBMF)—that explores potential predictive biomarkers in an automated, systematic, and unbiased manner. Applied retrospectively to real clinicogenomic datasets, particularly for immuno-oncology (IO) trials, our algorithm identifies biomarkers of IO-treated individuals who survive longer than those treated with other therapies. We demonstrate how our framework retrospectively contributes to a phase 3 clinical trial by uncovering a predictive, interpretable biomarker based solely on early study data. Patients identified with this predictive biomarker show a 15% improvement in survival risk compared to those in the original trial. The PBMF offers a general-purpose, rapid, and robust approach to inform biomarker strategy, providing actionable outcomes for clinical decision-making.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"263 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841637","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

Learning the language of T cell receptors through large-scale screening 通过大规模筛选学习 T 细胞受体的语言

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.032

Živa Moravec, John B.A.G. Haanen, Ton N. Schumacher, Wouter Scheper

引用次数: 0

Circular RMST cooperates with lineage-driving transcription factors to govern neuroendocrine transdifferentiation 环状RMST与谱系驱动转录因子共同调控神经内分泌转分化

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.027

Mona Teng, Jiacheng Guo, Xin Xu, Xinpei Ci, Yulin Mo, Yakup Kohen, Zuyao Ni, Sujun Chen, Wang Yuan Guo, Martin Bakht, Shengyu Ku, Michael Sigouros, Wenqin Luo, Colette Maya Macarios, Ziting Xia, Moliang Chen, Sami Ul Haq, Wen Yang, Alejandro Berlin, Theo van der Kwast, Housheng Hansen He

{"title":"Circular RMST cooperates with lineage-driving transcription factors to govern neuroendocrine transdifferentiation","authors":"Mona Teng, Jiacheng Guo, Xin Xu, Xinpei Ci, Yulin Mo, Yakup Kohen, Zuyao Ni, Sujun Chen, Wang Yuan Guo, Martin Bakht, Shengyu Ku, Michael Sigouros, Wenqin Luo, Colette Maya Macarios, Ziting Xia, Moliang Chen, Sami Ul Haq, Wen Yang, Alejandro Berlin, Theo van der Kwast, Housheng Hansen He","doi":"10.1016/j.ccell.2025.03.027","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.027","url":null,"abstract":"Circular RNA (circRNA) is a class of noncoding RNA with regulatory potentials. Its role in the transdifferentiation of prostate and lung adenocarcinoma into neuroendocrine prostate cancer (NEPC) and small cell lung cancer (SCLC) remains unexplored. Here, we identified circRMST as an exceptionally abundant circRNA predominantly expressed in NEPC and SCLC, with strong conservation between humans and mice. Functional studies using shRNA, siRNA, CRISPR-Cas13, and Cas9 consistently demonstrate that circRMST is essential for tumor growth and the expression of ASCL1, a master regulator of neuroendocrine fate. Genetic knockout of Rmst in NEPC genetic engineered mouse models prevents neuroendocrine transdifferentiation, maintaining tumors in an adenocarcinoma state. Mechanistically, circRMST physically interacts with lineage transcription factors NKX2-1 and SOX2. Loss of circRMST induces NKX2-1 protein degradation through autophagy-lysosomal pathway and alters the genomic binding of SOX2, collectively leading to the loss of ASCL1 transcription.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"18 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841635","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

Complexity of insulin resistance in early-onset colorectal cancer 早发性结直肠癌胰岛素抵抗的复杂性

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.033

Samson Mathews Samuel, Elizabeth Varghese, Dietrich Büsselberg

引用次数: 0