Cancer CellPub Date : 2025-06-12DOI: 10.1016/j.ccell.2025.05.013
David Stahl, Philipp Gödel, Hyatt Balke-Want, Rahil Gholamipoorfard, Paul Segbers, Luis Tetenborg, Mirjam Koker, Janina Dörr, Lisa Gregor, Daniel Bachurski, France Rose, Adrian G. Simon, Zinaida Good, Josefine Jakob, Björn Häupl, Marieke Nill, Ruth Flümann, Tobias Riet, Dinah Lange, Stuart J. Blakemore, Roland T. Ullrich
{"title":"CSF1R+ myeloid-monocytic cells drive CAR-T cell resistance in aggressive B cell lymphoma","authors":"David Stahl, Philipp Gödel, Hyatt Balke-Want, Rahil Gholamipoorfard, Paul Segbers, Luis Tetenborg, Mirjam Koker, Janina Dörr, Lisa Gregor, Daniel Bachurski, France Rose, Adrian G. Simon, Zinaida Good, Josefine Jakob, Björn Häupl, Marieke Nill, Ruth Flümann, Tobias Riet, Dinah Lange, Stuart J. Blakemore, Roland T. Ullrich","doi":"10.1016/j.ccell.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.013","url":null,"abstract":"Despite the improvement, approximately 60% of patients with relapsed or refractory (r/r) aggressive B cell lymphoma (B-NHL) do not achieve durable benefit from CAR-T cell therapy. To elucidate factors associated with CAR-T therapy resistance, we conducted high-dimensional analyses of pre- and post-CAR-T cell specimens. In patients with non-durable response, we identified a prognostically relevant lymphoma-associated myeloid-monocytic (LAMM) gene signature. In-depth profiling revealed a distinct CSF1R<sup>+</sup>CD14<sup>+</sup>CD68<sup>+</sup> LAMM cell population in both human and murine B-NHL that inhibits CAR-T cell function and correlates with poor outcome. Cell-cell inference analysis uncovered that LAMM cells impair CAR-T cell function through a direct LAMM-T cell interaction via the PGE<sub>2</sub>-EP2/EP4 axis. In an autochthonous lymphoma mouse model, combined anti-CD19 CAR-T cell therapy with CSF1R blockade exhibited synergistic effects and improved survival. These findings provide strong rationale for combining anti-CD19 CAR-T cells with CSF1R inhibitors in treating r/r aggressive B-NHL patients.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"12 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268964","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 : 2025-06-12DOI: 10.1016/j.ccell.2025.05.010
Benoit Rousseau, Mitesh Patel, Oliver Artz, Georgios Vlachos, Shrey Patel, Omar Hayatt, Guillem Argilés, Michael B. Foote, Lingqi Luo, Rachna Shah, Shub Mehta, Karthik Rangavajhula, Caitlin- M. Stewart, Drew Gerber, Rohini Bhattacharya, Dennis Stephens, David Mieles, Violaine Randrian, Somer Abdelfattah, Lin Zhang, Luis A. Diaz
{"title":"Induction of a mismatch repair deficient genotype by tailored chemical mutagenesis in experimental models of cancer","authors":"Benoit Rousseau, Mitesh Patel, Oliver Artz, Georgios Vlachos, Shrey Patel, Omar Hayatt, Guillem Argilés, Michael B. Foote, Lingqi Luo, Rachna Shah, Shub Mehta, Karthik Rangavajhula, Caitlin- M. Stewart, Drew Gerber, Rohini Bhattacharya, Dennis Stephens, David Mieles, Violaine Randrian, Somer Abdelfattah, Lin Zhang, Luis A. Diaz","doi":"10.1016/j.ccell.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.010","url":null,"abstract":"Mismatch repair deficient (MMRd) tumors harbor thousands of somatic mutations enriched for insertion–deletion (indels) conferring high sensitivity to immunotherapy. We sought to reproduce this phenotype using mutagenic agents to engineer an MMRd genotype in immunoresistant cells. The combination of temozolomide (TMZ) and cisplatin led to a rapid accumulation of a high mutational load enriched for indels in murine cell lines resulting from the epigenetic loss of <em>Msh2</em>. Pretreated cells showed sensitivity to PD-1 blockade. Systemic treatment with TMZ, cisplatin, and anti-PD-1 bearing immunoresistant tumor cells led to increased survival, intratumoral T cell infiltration, and downregulation of <em>Msh2</em> expression without affecting healthy tissues. In a clinical trial with 18 patients with refractory mismatch repair proficient colorectal cancer, no responses were seen, but MMRd signatures emerged in cell-free DNA. These findings show that recapitulating an MMRd genotype through chemical mutagenesis can generate an immunogenic phenotype.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"26 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268966","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 : 2025-06-09DOI: 10.1016/j.ccell.2025.05.009
Kevin Bi, Meng Xiao He, Ziad Bakouny, Abhay Kanodia, Sara Napolitano, Jingyi Wu, Grace Grimaldi, David A. Braun, Michael S. Cuoco, Angie Mayorga, Laura DelloStritto, Gabrielle Bouchard, John Steinharter, Alok K. Tewari, Natalie I. Vokes, Erin Shannon, Maxine Sun, Jihye Park, Steven L. Chang, Bradley A. McGregor, Eliezer M. Van Allen
{"title":"Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma","authors":"Kevin Bi, Meng Xiao He, Ziad Bakouny, Abhay Kanodia, Sara Napolitano, Jingyi Wu, Grace Grimaldi, David A. Braun, Michael S. Cuoco, Angie Mayorga, Laura DelloStritto, Gabrielle Bouchard, John Steinharter, Alok K. Tewari, Natalie I. Vokes, Erin Shannon, Maxine Sun, Jihye Park, Steven L. Chang, Bradley A. McGregor, Eliezer M. Van Allen","doi":"10.1016/j.ccell.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.009","url":null,"abstract":"(Cancer Cell <em>39</em>, 649–661.e1–e5; May 10, 2021)","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"17 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237992","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 : 2025-06-05DOI: 10.1016/j.ccell.2025.05.006
Alexander Benton, Jiageng Liu, Mathilde A. Poussin, Andrea Lang Goldgewicht, Madhara Udawela, Adham S. Bear, Nils Wellhausen, Beatriz M. Carreno, Pete M. Smith, Matthew D. Beasley, Ben R. Kiefel, Daniel J. Powell
{"title":"Mutant KRAS peptide targeted CAR-T cells engineered for cancer therapy","authors":"Alexander Benton, Jiageng Liu, Mathilde A. Poussin, Andrea Lang Goldgewicht, Madhara Udawela, Adham S. Bear, Nils Wellhausen, Beatriz M. Carreno, Pete M. Smith, Matthew D. Beasley, Ben R. Kiefel, Daniel J. Powell","doi":"10.1016/j.ccell.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.006","url":null,"abstract":"Despite the success of chimeric antigen receptor (CAR)-T cell therapies in hematological malignancies, clinical success against solid tumors is limited due to low therapeutic efficacy or dose-limiting toxicity. Developing therapies that trigger potent, yet manageable, immune responses capable of eliminating highly heterogeneous and immunosuppressive tumor cell populations remains a key challenge. Here, we harness multiple genetic approaches to develop a CAR-T cell therapy targeting tumors. First, we screen binders targeting oncogenic KRAS G12V mutations presented by peptide-MHC complexes. Subsequently, we incorporate these neoantigen binders into CAR-T cells (mKRAS NeoCARs) and demonstrate their efficacy in xenograft models of metastatic lung, pancreatic, and renal cell cancer. Finally, we enhance the <em>in vivo</em> efficacy and safety profile of mKRAS NeoCARs via inducible secretion of IL-12 and T cell receptor deletion. Together, these screening and engineering processes provide a modular platform for expanding the therapeutic index of cellular immunotherapies that target cancer.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"12 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219080","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 : 2025-06-05DOI: 10.1016/j.ccell.2025.05.005
Lihui Dong, Lai Guan Ng
{"title":"Tumor neutrophils rewired from birth","authors":"Lihui Dong, Lai Guan Ng","doi":"10.1016/j.ccell.2025.05.005","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.005","url":null,"abstract":"Systemic responses during tumor progression reshape granulopoiesis. In this issue of <em>Cancer Cell</em>, Garner et al. show that tumor-derived signals reprogram neutrophil development early in myelopoiesis. IL-1β blockade restores granulopoiesis, reverses neutrophil immunosuppressive imprinting, and reduces metastasis, highlighting a promising strategy for targeting neutrophil plasticity in cancer.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"456 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219066","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 : 2025-06-05DOI: 10.1016/j.ccell.2025.05.008
Jiachen Hu, Xuejun Jiang
{"title":"When essential metal elements become culprits—Cuproptosis in focus","authors":"Jiachen Hu, Xuejun Jiang","doi":"10.1016/j.ccell.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.008","url":null,"abstract":"Recently, a copper-dependent form of cell death called cuproptosis has been described, distinct from apoptosis, ferroptosis, and other known pathways. Cuproptosis is defined by excessive copper binding to lipoylated proteins, causing their aggregation and leading to cell death. Here, we discuss recent advances in understanding cuproptosis, focusing on its molecular mechanisms, physiological regulators, and therapeutic potential in cancer.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"5 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219078","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 : 2025-05-29DOI: 10.1016/j.ccell.2025.05.003
Jaco C. Knol, Mengge Lyu, Franziska Böttger, Madalena Nunes Monteiro, Thang V. Pham, Frank Rolfs, Andrea Vallés-Martí, Tim Schelfhorst, Richard R. de Goeij-de Haas, Irene V. Bijnsdorp, Shuaiyao Wang, Fangfei Zhang, Jun A, Bart A. Westerman, Barbara Sitek, Janne Lehtiö, Jan Koster, Jan N.M. IJzermans, Hanneke W.M. van Laarhoven, Maarten F. Bijlsma, Connie R. Jimenez
{"title":"The pan-cancer proteome atlas, a mass spectrometry-based landscape for discovering tumor biology, biomarkers, and therapeutic targets","authors":"Jaco C. Knol, Mengge Lyu, Franziska Böttger, Madalena Nunes Monteiro, Thang V. Pham, Frank Rolfs, Andrea Vallés-Martí, Tim Schelfhorst, Richard R. de Goeij-de Haas, Irene V. Bijnsdorp, Shuaiyao Wang, Fangfei Zhang, Jun A, Bart A. Westerman, Barbara Sitek, Janne Lehtiö, Jan Koster, Jan N.M. IJzermans, Hanneke W.M. van Laarhoven, Maarten F. Bijlsma, Connie R. Jimenez","doi":"10.1016/j.ccell.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.003","url":null,"abstract":"Most cancer proteomics studies to date have focused on a single cancer type. We report The Pan-Cancer Proteome Atlas (TPCPA) based on data-independent acquisition mass spectrometry, to better understand cancer biology and identify therapeutic targets and biomarkers. TPCPA includes 9,670 proteins derived from 999 primary tumors representing 22 cancer types. We describe pan-cancer and cancer type-enriched proteins with extensive external annotation, prioritizing candidate drug targets and biomarkers. Relevant for proteolysis-targeting chimeras, we identify E3-ubiquitin ligases highly expressed in specific tumor types, including HERC5 (esophageal cancer) and RNF5 (liver cancer). Co-expression analysis reveals 13 modules, including unexpected hub proteins as potential drug targets (e.g., GFPT1, LRPPRC, PINK1, DOCK2, and PTPN6). Analysis of 195 colorectal cancers identifies protein markers for RNA-based consensus molecular subtypes (CMSs) and two immune subtypes with prognostic value. We report a cancer type classifier for identification of cancers of unknown primary origin. All TPCPA data can be queried in a dedicated web resource.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"31 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165276","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 : 2025-05-29DOI: 10.1016/j.ccell.2025.05.002
Andrew W. Daman, Anthony C. Antonelli, Gil Redelman-Sidi, Lucinda Paddock, Shireen Khayat, Mythili Ketavarapu, Jin Gyu Cheong, Leonardo F. Jurado, Anna Benjamin, Song Jiang, Dughan Ahimovic, Victoria R. Lawless, Michael J. Bale, Oleg Loutochin, Victor A. McPherson, Maziar Divangahi, Rachel E. Niec, Dana Pe’er, Eugene Pietzak, Steven Z. Josefowicz, Michael S. Glickman
{"title":"Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven anti-tumor immunity","authors":"Andrew W. Daman, Anthony C. Antonelli, Gil Redelman-Sidi, Lucinda Paddock, Shireen Khayat, Mythili Ketavarapu, Jin Gyu Cheong, Leonardo F. Jurado, Anna Benjamin, Song Jiang, Dughan Ahimovic, Victoria R. Lawless, Michael J. Bale, Oleg Loutochin, Victor A. McPherson, Maziar Divangahi, Rachel E. Niec, Dana Pe’er, Eugene Pietzak, Steven Z. Josefowicz, Michael S. Glickman","doi":"10.1016/j.ccell.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.002","url":null,"abstract":"<em>Mycobacterium bovis</em> Bacillus Calmette-Guérin (BCG) is the vaccine against tuberculosis and an immunotherapy for bladder cancer. When administered intravenously, BCG reprograms bone marrow hematopoietic stem and progenitor cells (HSPCs), leading to heterologous protection against infections. Whether HSPC reprogramming contributes to the anti-tumor effects of BCG administered into the bladder is unknown. We demonstrate that BCG administered in the bladder colonizes the bone marrow and, in both mice and humans, reprograms HSPCs to alter and amplify myelopoiesis. BCG-reprogrammed HSPCs are sufficient to confer augmented anti-tumor immunity through production of neutrophils, monocytes, and dendritic cells that broadly remodel the tumor microenvironment, drive T cell-dependent anti-tumor responses, and synergize with checkpoint blockade. We conclude that bladder BCG acts systemically through hematopoiesis, highlighting the broad potential of HSPC reprogramming to enhance the innate drivers of T cell-dependent tumor immunity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"29 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165271","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 : 2025-05-27DOI: 10.1016/j.ccell.2025.05.007
Toshiro Hara, Rony Chanoch-Myers, Nathan D. Mathewson, Chad Myskiw, Lyla Atta, Lillian Bussema, Stephen W. Eichhorn, Alissa C. Greenwald, Gabriela S. Kinker, Christopher Rodman, L. Nicolas Gonzalez Castro, Hiroaki Wakimoto, Orit Rozenblatt-Rosen, Xiaowei Zhuang, Jean Fan, Tony Hunter, Inder M. Verma, Kai W. Wucherpfennig, Aviv Regev, Mario L. Suvà, Itay Tirosh
{"title":"Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma","authors":"Toshiro Hara, Rony Chanoch-Myers, Nathan D. Mathewson, Chad Myskiw, Lyla Atta, Lillian Bussema, Stephen W. Eichhorn, Alissa C. Greenwald, Gabriela S. Kinker, Christopher Rodman, L. Nicolas Gonzalez Castro, Hiroaki Wakimoto, Orit Rozenblatt-Rosen, Xiaowei Zhuang, Jean Fan, Tony Hunter, Inder M. Verma, Kai W. Wucherpfennig, Aviv Regev, Mario L. Suvà, Itay Tirosh","doi":"10.1016/j.ccell.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.007","url":null,"abstract":"(Cancer Cell <em>39</em>, 779–792.e1–e11; June 14, 2021)","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"239 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145856","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 : 2025-05-15DOI: 10.1016/j.ccell.2025.04.014
Shiekh Tanveer Ahmad, Yiran Li, Jesus Garcia-Lopez, Brian L. Gudenas, Jennifer Hadley, Leena Paul, Stephanie C. Wu, Alaa Refaat, Marija Kojic, Melissa Batts, Taha Soliman, Aaron Pitre, Frederik Arnskötter, Frederique Zindy, Alun Jones, Nathaniel R. Twarog, Anand Mayasundari, Brandon Bianski, Christopher Tinkle, Abbas Shirinifard, Paul A. Northcott
{"title":"Genetic modeling of ELP1-associated Sonic hedgehog medulloblastoma identifies MDM2 as a selective therapeutic target","authors":"Shiekh Tanveer Ahmad, Yiran Li, Jesus Garcia-Lopez, Brian L. Gudenas, Jennifer Hadley, Leena Paul, Stephanie C. Wu, Alaa Refaat, Marija Kojic, Melissa Batts, Taha Soliman, Aaron Pitre, Frederik Arnskötter, Frederique Zindy, Alun Jones, Nathaniel R. Twarog, Anand Mayasundari, Brandon Bianski, Christopher Tinkle, Abbas Shirinifard, Paul A. Northcott","doi":"10.1016/j.ccell.2025.04.014","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.014","url":null,"abstract":"Germline loss-of-function (LOF) variants in <em>Elongator acetyltransferase complex subunit 1 (ELP1)</em> are the most prevalent predisposing genetic events in childhood medulloblastoma (MB), accounting for ∼30% of the Sonic hedgehog (SHH) 3 subtype. The mechanism(s) by which germline <em>ELP1</em> deficiency provokes SHH-MB pathogenesis remain unknown. Genetically engineered mice mimicking heterozygous <em>Elp1</em> LOF (<em>Elp1</em><sub><em>HET</em></sub><em>)</em> seen in affected germline carriers exhibit hallmark features of premalignancy in cerebellar granule neuron progenitors (GNPs), including increased DNA replication stress, genomic instability, accelerated cell cycle, and stalled differentiation. Orthotopic transplantation of <em>Elp1</em><sub><em>HET</em></sub> GNPs harboring somatic <em>Ptch1</em> inactivation yields SHH-MB-like tumors with compromised p53 signaling, providing a plausible explanation for the exclusivity of <em>ELP1-</em>associated MBs in the SHH-3 subtype. Preclinical treatment of <em>ELP1</em>-mutant patient-derived xenografts with an FDA-approved MDM2 inhibitor reactivates p53-dependent apoptosis and extends survival. Our findings functionally substantiate the role of <em>ELP1</em> deficiency in SHH-MB predisposition and nominate therapeutics targeting MDM2 as a rational treatment option.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"13 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980018","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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