Cancer discoveryPub Date : 2025-05-07DOI: 10.1158/2159-8290.CD-24-1532
Wei Lv, Yuchen Zeng, Conghui Li, Yuan Liang, Huiying Tao, Yanfen Zhu, Xiaolong Sui, Yue Li, Shiqi Jiang, Qingqing Gao, Elias Rodriguez-Fos, Gino Prasad, Yuanmei Wang, Run Zhou, Zhe Xu, Xiaoguang Pan, Linlin Chen, Xi Xiang, Huajing Teng, Chaoyang Sun, Tianyu Qin, Wei Dong, Yongwei Li, Xun Lan, Xuesong Li, Lin Lin, Lars Bolund, Huanming Yang, Roel G W Verhaak, Bishoy M Faltas, Jacob B Hansen, Sihan Wu, Paul S Mischel, Anton G Henssen, Vineet Bafna, Jens Luebeck, Birgitte Regenberg, Yonglun Luo, Chunhua Lin, Peng Han
{"title":"Spatial-Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment.","authors":"Wei Lv, Yuchen Zeng, Conghui Li, Yuan Liang, Huiying Tao, Yanfen Zhu, Xiaolong Sui, Yue Li, Shiqi Jiang, Qingqing Gao, Elias Rodriguez-Fos, Gino Prasad, Yuanmei Wang, Run Zhou, Zhe Xu, Xiaoguang Pan, Linlin Chen, Xi Xiang, Huajing Teng, Chaoyang Sun, Tianyu Qin, Wei Dong, Yongwei Li, Xun Lan, Xuesong Li, Lin Lin, Lars Bolund, Huanming Yang, Roel G W Verhaak, Bishoy M Faltas, Jacob B Hansen, Sihan Wu, Paul S Mischel, Anton G Henssen, Vineet Bafna, Jens Luebeck, Birgitte Regenberg, Yonglun Luo, Chunhua Lin, Peng Han","doi":"10.1158/2159-8290.CD-24-1532","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-24-1532","url":null,"abstract":"<p><strong>Significance: </strong>Our comprehensive analysis of ecDNA in urothelial carcinoma reveals its crucial role in driving the evolution and heterogeneity of multifocal cancer, as well as its early involvement in tumorigenesis. Moreover, this study sheds light on immune evasion mechanisms associated with ecDNA and offers valuable insights for developing targeted therapeutic strategies.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1-OF22"},"PeriodicalIF":29.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982811","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}
{"title":"GPR65 Inactivation in Tumor Cells Drives Antigen-Independent CAR T-cell Resistance via Macrophage Remodeling.","authors":"Jayadev Mavuluri, Yogesh Dhungana, Lindsay L Jones, Sheetal Bhatara, Hao Shi, Xu Yang, Song-Eun Lim, Noemi Reyes, Hongbo Chi, Jiyang Yu, Terrence L Geiger","doi":"10.1158/2159-8290.CD-24-0841","DOIUrl":"10.1158/2159-8290.CD-24-0841","url":null,"abstract":"<p><strong>Significance: </strong>The study identifies GPR65 as an important determinant of B-cell acute lymphoblastic leukemia response to CAR T-cell therapy. Notably, GPR65 absence signals CAR T resistance. By emphasizing the therapeutic potential of targeting VEGFA or host macrophages, our study identifies routes to optimize CAR T-cell therapy outcomes in hematologic malignancies via tumor microenvironment manipulation.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"1018-1036"},"PeriodicalIF":29.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490861","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}
Cancer discoveryPub Date : 2025-05-02DOI: 10.1158/2159-8290.cd-25-0099
Kok Haw Jonathan Lim,Zayd Tippu,Pippa G Corrie,Michael Hubank,James Larkin,Trevor D Lawley,Mark Stares,Grant D Stewart,Amy Strange,Stefan N Symeonides,Bernadett Szabados,Nicholas C Turner,Tom Waddell,Santiago Zelenay,Manuel Salto-Tellez,Caroline Dive,Samra Turajlic,
{"title":"MANIFEST: Multiomic Platform for Cancer Immunotherapy.","authors":"Kok Haw Jonathan Lim,Zayd Tippu,Pippa G Corrie,Michael Hubank,James Larkin,Trevor D Lawley,Mark Stares,Grant D Stewart,Amy Strange,Stefan N Symeonides,Bernadett Szabados,Nicholas C Turner,Tom Waddell,Santiago Zelenay,Manuel Salto-Tellez,Caroline Dive,Samra Turajlic,","doi":"10.1158/2159-8290.cd-25-0099","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0099","url":null,"abstract":"Immunotherapy has revolutionized survival outcomes for many patients diagnosed with cancer. However, biomarkers that can reliably distinguish treatment responders from nonresponders, predict potential life-threatening and life-changing drug-induced toxicities, or rationalize treatment choices are still lacking. In response to this unmet clinical need, we introduce Multiomic ANalysis of Immunotherapy Features Evidencing Success and Toxicity, a tumor type-agnostic platform to provide deep profiling of patients receiving immunotherapy that will enable integrative identification of biomarkers and discovery of novel targets using artificial intelligence and machine learning.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"118 1","pages":"878-883"},"PeriodicalIF":28.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902903","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 discoveryPub Date : 2025-05-02DOI: 10.1158/2159-8290.CD-23-0882
Takafumi N Yamaguchi, Kathleen E Houlahan, Helen Zhu, Natalie Kurganovs, Julie Livingstone, Natalie S Fox, Jiapei Yuan, Jocelyn Sietsma Penington, Chol-Hee Jung, Tommer Schwarz, Weerachai Jaratlerdsiri, Job van Riet, Peter Georgeson, Stefano Mangiola, Kodi Taraszka, Robert Lesurf, Jue Jiang, Ken Chow, Lawrence E Heisler, Yu-Jia Shiah, Susmita G Ramanand, Michael J Clarkson, Anne Nguyen, Shadrielle Melijah G Espiritu, Ryan Stuchbery, Richard Jovelin, Vincent Huang, Connor Bell, Edward O'Connor, Patrick J McCoy, Christopher M Lalansingh, Marek Cmero, Adriana Salcedo, Eva K F Chan, Lydia Y Liu, Phillip D Stricker, Vinayak Bhandari, Riana M S Bornman, Dorota H S Sendorek, Andrew Lonie, Stephenie D Prokopec, Michael Fraser, Justin S Peters, Adrien Foucal, Shingai B A Mutambirwa, Lachlan Mcintosh, Michèle Orain, Matthew Wakefield, Valérie Picard, Daniel J Park, Hélène Hovington, Michael Kerger, Alain Bergeron, Veronica Sabelnykova, Ji-Heui Seo, Mark M Pomerantz, Noah Zaitlen, Sebastian M Waszak, Alexander Gusev, Louis Lacombe, Yves Fradet, Andrew Ryan, Amar U Kishan, Martijn P Lolkema, Joachim Weischenfeldt, Bernard Têtu, Anthony J Costello, Vanessa M Hayes, Rayjean J Hung, Housheng H He, John D McPherson, Bogdan Pasaniuc, Theodorus van der Kwast, Anthony T Papenfuss, Matthew L Freedman, Bernard J Pope, Robert G Bristow, Ram S Mani, Niall M Corcoran, Jüri Reimand, Christopher M Hovens, Paul C Boutros
{"title":"The Germline and Somatic Origins of Prostate Cancer Heterogeneity.","authors":"Takafumi N Yamaguchi, Kathleen E Houlahan, Helen Zhu, Natalie Kurganovs, Julie Livingstone, Natalie S Fox, Jiapei Yuan, Jocelyn Sietsma Penington, Chol-Hee Jung, Tommer Schwarz, Weerachai Jaratlerdsiri, Job van Riet, Peter Georgeson, Stefano Mangiola, Kodi Taraszka, Robert Lesurf, Jue Jiang, Ken Chow, Lawrence E Heisler, Yu-Jia Shiah, Susmita G Ramanand, Michael J Clarkson, Anne Nguyen, Shadrielle Melijah G Espiritu, Ryan Stuchbery, Richard Jovelin, Vincent Huang, Connor Bell, Edward O'Connor, Patrick J McCoy, Christopher M Lalansingh, Marek Cmero, Adriana Salcedo, Eva K F Chan, Lydia Y Liu, Phillip D Stricker, Vinayak Bhandari, Riana M S Bornman, Dorota H S Sendorek, Andrew Lonie, Stephenie D Prokopec, Michael Fraser, Justin S Peters, Adrien Foucal, Shingai B A Mutambirwa, Lachlan Mcintosh, Michèle Orain, Matthew Wakefield, Valérie Picard, Daniel J Park, Hélène Hovington, Michael Kerger, Alain Bergeron, Veronica Sabelnykova, Ji-Heui Seo, Mark M Pomerantz, Noah Zaitlen, Sebastian M Waszak, Alexander Gusev, Louis Lacombe, Yves Fradet, Andrew Ryan, Amar U Kishan, Martijn P Lolkema, Joachim Weischenfeldt, Bernard Têtu, Anthony J Costello, Vanessa M Hayes, Rayjean J Hung, Housheng H He, John D McPherson, Bogdan Pasaniuc, Theodorus van der Kwast, Anthony T Papenfuss, Matthew L Freedman, Bernard J Pope, Robert G Bristow, Ram S Mani, Niall M Corcoran, Jüri Reimand, Christopher M Hovens, Paul C Boutros","doi":"10.1158/2159-8290.CD-23-0882","DOIUrl":"10.1158/2159-8290.CD-23-0882","url":null,"abstract":"<p><strong>Significance: </strong>This study uncovered 223 recurrently mutated driver regions using the largest cohort of prostate tumors to date. It reveals associations between germline SNPs, somatic drivers, and tumor aggression, offering significant insights into how prostate tumor evolution is shaped by germline factors and the timing of somatic mutations.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"988-1017"},"PeriodicalIF":29.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405678","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}
Cancer discoveryPub Date : 2025-05-02DOI: 10.1158/2159-8290.cd-25-0209
Ken Furudate, Koichi Takahashi
{"title":"Prenatal Chemotherapy and Its Impact on the Genome of Fetal Hematopoiesis","authors":"Ken Furudate, Koichi Takahashi","doi":"10.1158/2159-8290.cd-25-0209","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0209","url":null,"abstract":"Summary: The genotoxic impact of cancer chemotherapy administered during pregnancy on neonatal hematopoietic cells remains largely unknown. In this study, Struys and colleagues demonstrate that prenatal chemotherapy exposure leads to an increased somatic mutational burden in neonatal hematopoietic stem and progenitor cells, characterized by distinct mutational signatures, revealing a previously unrecognized consequence of in utero chemotherapy on fetal hematopoiesis and underscoring the need for further research to assess its long-term implications and potential risks. See related article by Struys et al., p. 903","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"34 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901254","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 discoveryPub Date : 2025-05-02DOI: 10.1158/2159-8290.CD-25-0262
Alessandra Vaccaro, Zahraa Rahal, Humam Kadara, Tina Cascone
{"title":"A Roadmap to Precision Immunotherapy for Early-Stage Non-Small Cell Lung Cancer.","authors":"Alessandra Vaccaro, Zahraa Rahal, Humam Kadara, Tina Cascone","doi":"10.1158/2159-8290.CD-25-0262","DOIUrl":"10.1158/2159-8290.CD-25-0262","url":null,"abstract":"<p><p>Immunotherapy has revolutionized the treatment of early-stage non-small cell lung cancer; yet many patients fail to achieve long-lasting benefit, partially because of incomplete or inconsistent biomarker predictions. Integrative multiomics, combining tumor-intrinsic, immune microenvironment, and systemic factors, offer a more comprehensive framework for precision immunotherapy, enabling improved patient stratification, treatment selection and outcomes.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"884-889"},"PeriodicalIF":29.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490860","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 discoveryPub Date : 2025-05-02DOI: 10.1158/2159-8290.CD-24-0991
Miya B Hugaboom, Lena V Wirth, Kelly Street, Neil Ruthen, Opeyemi A Jegede, Nicholas R Schindler, Valisha Shah, Jacob P Zaemes, Nourhan El Ahmar, Sayed Matar, Varunika Savla, Toni K Choueiri, Thomas Denize, Destiny J West, David F McDermott, Elizabeth R Plimack, Jeffrey A Sosman, Naomi B Haas, Mark N Stein, Robert Alter, Mehmet A Bilen, Michael E Hurwitz, Hans Hammers, Sabina Signoretti, Michael B Atkins, Catherine J Wu, David A Braun
{"title":"Presence of Tertiary Lymphoid Structures and Exhausted Tissue-Resident T Cells Determines Clinical Response to PD-1 Blockade in Renal Cell Carcinoma.","authors":"Miya B Hugaboom, Lena V Wirth, Kelly Street, Neil Ruthen, Opeyemi A Jegede, Nicholas R Schindler, Valisha Shah, Jacob P Zaemes, Nourhan El Ahmar, Sayed Matar, Varunika Savla, Toni K Choueiri, Thomas Denize, Destiny J West, David F McDermott, Elizabeth R Plimack, Jeffrey A Sosman, Naomi B Haas, Mark N Stein, Robert Alter, Mehmet A Bilen, Michael E Hurwitz, Hans Hammers, Sabina Signoretti, Michael B Atkins, Catherine J Wu, David A Braun","doi":"10.1158/2159-8290.CD-24-0991","DOIUrl":"10.1158/2159-8290.CD-24-0991","url":null,"abstract":"<p><strong>Significance: </strong>We describe a paradigm wherein combined high TLS and low tissue-resident exhausted CD8+ T cells are required for optimal response to PD-1 blockade in RCC. This analysis identifies key determinants of response to PD-1 blockade in advanced RCC and suggests avenues for future immune modulation through rational combination therapy strategies.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"948-968"},"PeriodicalIF":29.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482121","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}
Cancer discoveryPub Date : 2025-04-30DOI: 10.1158/2159-8290.cd-25-0175
Frank S Lee
{"title":"Under (Genetic Selection) Pressure: Human Tumors and Human Populations in Hypoxia.","authors":"Frank S Lee","doi":"10.1158/2159-8290.cd-25-0175","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0175","url":null,"abstract":"Arenillas and colleagues report that pheochromocytomas and paragangliomas in the setting of chronic hypoxia due to cyanotic congenital heart disease harbor, at high frequency, somatic gain-of-function mutations in the EPAS1 gene, which encodes for one of the oxygen-labile subunits of the hypoxia-inducible factor complex. Interestingly, germline loss-of-function EPAS1 alleles are under natural selection in human populations subjected to a different chronic hypoxia condition, namely, high altitude. See related article by Arenillas et al., p. XX.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"11 1","pages":"OF1-OF3"},"PeriodicalIF":28.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893145","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 discoveryPub Date : 2025-04-30DOI: 10.1158/2159-8290.cd-25-0212
Aleksandr Dolskii,Edna Cukierman
{"title":"FABP4-tastic Pancreatic Stellate Cells Coddle KITL to Uphold Inherent Microenvironmental Tumor Suppression.","authors":"Aleksandr Dolskii,Edna Cukierman","doi":"10.1158/2159-8290.cd-25-0212","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0212","url":null,"abstract":"Oñate and colleagues demonstrate that KITL expression in pancreatic stellate cells is crucial for maintaining the inherent tumor-suppressive function of the pancreatic microenvironment, and its loss enables pancreatic cancer development. This pivotal discovery not only reinforces the century-old hypothesis of natural microenvironmental tumor suppression but also highlights a promising therapeutic avenue whereby restoring KITL expression could reestablish the tumor-suppressive functions of pancreas-resident fibroblastic cells. See related article by Oñate et al., p. XX.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"19 1","pages":"OF1-OF3"},"PeriodicalIF":28.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893143","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 discoveryPub Date : 2025-04-29DOI: 10.1158/2159-8290.cd-25-0293
Kexin Koh,Rachel Scott,Elizabeth M Cespedes Feliciano,Tobias Janowitz,Marcus D Goncalves,Eileen P White,Barry J A Laird,Kerstin Haase,Mariam Jamal-Hanjani
{"title":"Cancer-Associated Cachexia: Bridging Clinical Findings with Mechanistic Insights in Human Studies.","authors":"Kexin Koh,Rachel Scott,Elizabeth M Cespedes Feliciano,Tobias Janowitz,Marcus D Goncalves,Eileen P White,Barry J A Laird,Kerstin Haase,Mariam Jamal-Hanjani","doi":"10.1158/2159-8290.cd-25-0293","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0293","url":null,"abstract":"CAC represents a significant clinical unmet need. Despite its high prevalence and associated mortality and morbidity, there are currently no globally approved effective therapies. This review provides a comprehensive overview of human studies aimed at defining CAC clinically and identifying mediators underlying it that are revealing effective health interventions. Furthermore, we highlight ongoing international efforts to advance our understanding of CAC.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"9 1","pages":"OF1-OF26"},"PeriodicalIF":28.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889321","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}
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