Cancer CellPub Date : 2026-08-03DOI: 10.1016/j.ccell.2026.07.003
Yang Zheng,Caleb Cheng,Yizhi Cao,Gabriel Cruz,Yuping Zhang,Radha Paturu,Somnath Mahapatra,Jing Hu,Rahul Mannan,Hüseyin Karabürk,Rupam Bhattacharyya,Yitong Yin,Yi Zhao,Wenyan Liu,Xuhong Cao,Hui Xue,Chungen Li,Zhen Wang,Stephanie J. Miner,Zachery R. Reichert,Rohit Mehra,Ulka Vaishampayan,Vaibhav Sahai,Lois S. Weisman,Ke Ding,Costas A. Lyssiotis,Yuzhuo Wang,Arul M. Chinnaiyan,Yuanyuan Qiao
{"title":"A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer","authors":"Yang Zheng,Caleb Cheng,Yizhi Cao,Gabriel Cruz,Yuping Zhang,Radha Paturu,Somnath Mahapatra,Jing Hu,Rahul Mannan,Hüseyin Karabürk,Rupam Bhattacharyya,Yitong Yin,Yi Zhao,Wenyan Liu,Xuhong Cao,Hui Xue,Chungen Li,Zhen Wang,Stephanie J. Miner,Zachery R. Reichert,Rohit Mehra,Ulka Vaishampayan,Vaibhav Sahai,Lois S. Weisman,Ke Ding,Costas A. Lyssiotis,Yuzhuo Wang,Arul M. Chinnaiyan,Yuanyuan Qiao","doi":"10.1016/j.ccell.2026.07.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.07.003","url":null,"abstract":"Neuroendocrine prostate cancer (NEPC) persists in a profoundly hypoxic microenvironment, yet the mechanisms enabling tumor adaptation to this metabolically challenging niche remain undefined. Here, we identify the lipid kinase PIKfyve as overexpressed in NEPC, functioning as a central node in a stress-adaptive lipid kinase axis that supports adaptation to persistent endoplasmic reticulum (ER) stress. Mechanistically, NEPC requires PIKfyve-mediated lysosomal degradation and lipid recycling to maintain metabolic homeostasis under hypoxia. PIKfyve inhibition disrupts lysosomal function, exacerbates ER stress, and activates a compensatory sterol regulatory element-binding protein (SREBP)-dependent de novo lipogenesis program essential for NEPC survival. This stress-lipid axis creates a synthetic vulnerability between PIKfyve and fatty acid synthase (FASN), where dual inhibition synergistically amplifies ER stress, triggers the terminal unfolded protein response, and induces tumor cell death. These findings reveal a metabolic adaptation in NEPC and provide preclinical evidence that co-targeting PIKfyve and FASN can overcome hypoxia-associated stress adaptation.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"1 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665984","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}
Cancer CellPub Date : 2026-07-17DOI: 10.1016/j.ccell.2026.07.009
Xiangqian Kong, Jie Chen, Wenbing Xie, Stephen M. Brown, Yi Cai, Kaichun Wu, Daiming Fan, Yongzhan Nie, Srinivasan Yegnasubramanian, Rochelle L. Tiedemann, Yong Tao, Ray-Whay Chiu Yen, Michael J. Topper, Cynthia A. Zahnow, Hariharan Easwaran, Scott B. Rothbart, Limin Xia, Stephen B. Baylin
{"title":"Defining UHRF1 Domains that Support Maintenance of Human Colon Cancer DNA Methylation and Oncogenic Properties","authors":"Xiangqian Kong, Jie Chen, Wenbing Xie, Stephen M. Brown, Yi Cai, Kaichun Wu, Daiming Fan, Yongzhan Nie, Srinivasan Yegnasubramanian, Rochelle L. Tiedemann, Yong Tao, Ray-Whay Chiu Yen, Michael J. Topper, Cynthia A. Zahnow, Hariharan Easwaran, Scott B. Rothbart, Limin Xia, Stephen B. Baylin","doi":"10.1016/j.ccell.2026.07.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.07.009","url":null,"abstract":"","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"71 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148460171","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}
Cancer CellPub Date : 2026-07-17DOI: 10.1016/j.ccell.2026.07.008
Limin Xia, Wenjie Huang, Marina Bellani, Michael M. Seidman, Kaichun Wu, Daiming Fan, Yongzhan Nie, Yi Cai, Yang W. Zhang, Li-Rong Yu, Huili Li, Cynthia A. Zahnow, Wenbing Xie, Ray-Whay Chiu Yen, Feyruz V. Rassool, Stephen B. Baylin
{"title":"CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes","authors":"Limin Xia, Wenjie Huang, Marina Bellani, Michael M. Seidman, Kaichun Wu, Daiming Fan, Yongzhan Nie, Yi Cai, Yang W. Zhang, Li-Rong Yu, Huili Li, Cynthia A. Zahnow, Wenbing Xie, Ray-Whay Chiu Yen, Feyruz V. Rassool, Stephen B. Baylin","doi":"10.1016/j.ccell.2026.07.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.07.008","url":null,"abstract":"","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"71 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148460348","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}
Cancer CellPub Date : 2026-07-17DOI: 10.1016/j.ccell.2026.07.005
Michael Quante, Govind Bhagat, Julian A. Abrams, Frederic Marache, Pamela Good, Michele D. Lee, Yoomi Lee, Richard Friedman, Samuel Asfaha, Zinaida Dubeykovskaya, Umar Mahmood, Jose-Luiz Figueiredo, Jan Kitajewski, Carrie Shawber, Charles J. Lightdale, Anil K. Rustgi, Timothy C. Wang
{"title":"Bile Acid and Inflammation Activate Gastric Cardia Stem Cells in a Mouse Model of Barrett-Like Metaplasia","authors":"Michael Quante, Govind Bhagat, Julian A. Abrams, Frederic Marache, Pamela Good, Michele D. Lee, Yoomi Lee, Richard Friedman, Samuel Asfaha, Zinaida Dubeykovskaya, Umar Mahmood, Jose-Luiz Figueiredo, Jan Kitajewski, Carrie Shawber, Charles J. Lightdale, Anil K. Rustgi, Timothy C. Wang","doi":"10.1016/j.ccell.2026.07.005","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.07.005","url":null,"abstract":"","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"33 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148460172","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}
Cancer CellPub Date : 2026-07-13Epub Date: 2026-06-11DOI: 10.1016/j.ccell.2026.05.009
Bastian Kruse, Ben P Leonhardt, Jan P Böttcher
{"title":"STING unlocks CD4⁺ T cell immunity in pancreatic cancer.","authors":"Bastian Kruse, Ben P Leonhardt, Jan P Böttcher","doi":"10.1016/j.ccell.2026.05.009","DOIUrl":"10.1016/j.ccell.2026.05.009","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinomas (PDACs) are lethal cancers resistant to immunotherapies. In this issue of Cancer Cell, Kureshi et al. show that combining checkpoint blockade with STING-mediated innate immune stimulation unlocks cDC2-driven CD4<sup>+</sup> T cell immunity in mice, promoting PDAC immune control. This cellular axis may be exploited for PDAC therapy.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1325-1326"},"PeriodicalIF":56.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223418","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}
Cancer CellPub Date : 2026-07-13Epub Date: 2026-06-11DOI: 10.1016/j.ccell.2026.05.011
Manon Bulliard, Yakov Perlov, Ömer H Yilmaz, Bing Shui
{"title":"High-plasticity oncofetal cell states in early pre-metastatic colorectal cancer.","authors":"Manon Bulliard, Yakov Perlov, Ömer H Yilmaz, Bing Shui","doi":"10.1016/j.ccell.2026.05.011","DOIUrl":"10.1016/j.ccell.2026.05.011","url":null,"abstract":"<p><p>In Nature, Buissant des Amorie et al. demonstrate that colorectal cancer acquires oncofetal cell states that resemble embryonic intestines, confer stem-like features, reshape epithelial identity, and prime cells for invasion and metastasis. Oncofetal cells are essential for metastasis and ubiquitous in non-metastatic tumors, with cancer-associated fibroblasts as key microenvironmental drivers.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1343-1345"},"PeriodicalIF":56.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223397","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}
Cancer CellPub Date : 2026-07-13Epub Date: 2026-06-25DOI: 10.1016/j.ccell.2026.06.002
Yingcheng Wu, Hao Xiao, Nan Jiang, Will Hua, Jiaqiang Ma, Jiacheng Ge, Yong Liu, Zhongyue Zhang, Jack Xiaoyu Chen, Ruofan Jin, Yingrui Wang, Jian Zhou, Jia Fan, Zaixiang Zheng, Lei Bai, Haifeng Ye, Qi Liu, Guoji Guo, Zaixi Zhang, Siqi Sun, Tiannan Guo, Shuangjia Zheng, Qiang Gao
{"title":"OpenIO: An open framework for AI-native immunotherapy.","authors":"Yingcheng Wu, Hao Xiao, Nan Jiang, Will Hua, Jiaqiang Ma, Jiacheng Ge, Yong Liu, Zhongyue Zhang, Jack Xiaoyu Chen, Ruofan Jin, Yingrui Wang, Jian Zhou, Jia Fan, Zaixiang Zheng, Lei Bai, Haifeng Ye, Qi Liu, Guoji Guo, Zaixi Zhang, Siqi Sun, Tiannan Guo, Shuangjia Zheng, Qiang Gao","doi":"10.1016/j.ccell.2026.06.002","DOIUrl":"10.1016/j.ccell.2026.06.002","url":null,"abstract":"<p><p>We propose Open Immune Oncology (OpenIO), a framework integrating generative AI and omics to advance precision oncology. By leveraging biological scaling laws and foundation models, we aim to transition immunotherapy from empirical screening to rational, AI-native engineering of therapeutic interventions.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1315-1320"},"PeriodicalIF":56.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327062","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}
Cancer CellPub Date : 2026-07-13Epub Date: 2026-06-25DOI: 10.1016/j.ccell.2026.06.004
Hilal Bashir, Katherine Z Sanidad, Purnima Ravisankar, Kelly M Banks, Avipsa Bose, Shui Yu, Joshua J C McGrath, Hannah C Carrow, Taeyul K Kim, Chloe A Troxell, Julia A Brown, Lucy R Hart, Jeremy Goc, Mikala Egeblad, Jayanta Chaudhuri, Han Sang Kim, Patrick C Wilson, David C Lyden, Irina R Matei, Naohiro Inohara, Gregory F Sonnenberg, Melody Y Zeng
{"title":"Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth.","authors":"Hilal Bashir, Katherine Z Sanidad, Purnima Ravisankar, Kelly M Banks, Avipsa Bose, Shui Yu, Joshua J C McGrath, Hannah C Carrow, Taeyul K Kim, Chloe A Troxell, Julia A Brown, Lucy R Hart, Jeremy Goc, Mikala Egeblad, Jayanta Chaudhuri, Han Sang Kim, Patrick C Wilson, David C Lyden, Irina R Matei, Naohiro Inohara, Gregory F Sonnenberg, Melody Y Zeng","doi":"10.1016/j.ccell.2026.06.004","DOIUrl":"10.1016/j.ccell.2026.06.004","url":null,"abstract":"<p><p>Chronic stress disrupts the gut microbiota in patients with cancer; however, how stress-induced microbiota perturbations impact anti-tumor immunity remains unclear. Here, we show that the gut microbiota is required for chronic stress-induced glucocorticoid production, which impairs antigen-specific germinal center B cell responses. In mouse models of colorectal cancer or melanoma, chronic stress promotes translocation of a gut pathobiont, Enterococcus gallinarum (Eg), to tumors. Within tumors, Eg phage DNA induces glucocorticoid production by cancer-associated fibroblasts (CAFs) via TLR9, which suppresses anti-tumor B cell responses through the glucocorticoid receptor. Targeting intratumoral TLR9 or Eg significantly lowers intratumor glucocorticoid levels and reverses the tumor-promoting effects of chronic stress. Extending these findings to human cancer, we identify lytic phages in a Klebsiella pneumoniae isolate from human colorectal tumors that promote tumor growth and detect phage DNA in human brain tumors. Together, our study reveals a chronic stress-induced intratumor phage-CAF-B cell circuit that weakens anti-tumor immunity.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1458-1476.e13"},"PeriodicalIF":56.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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