Cancer CellPub Date : 2025-04-24DOI: 10.1016/j.ccell.2025.03.034
Michael J. Dennis, Ravindra Uppaluri
{"title":"Easing cisplatin’s toll in nasopharyngeal carcinoma","authors":"Michael J. Dennis, Ravindra Uppaluri","doi":"10.1016/j.ccell.2025.03.034","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.034","url":null,"abstract":"Anti-PD-1 immune checkpoint inhibitors improve outcomes in relapsed/metastatic nasopharyngeal carcinoma (NPC). In this issue of <em>Cancer Cell</em>, Xu et al. achieved favorable outcomes by incorporating nivolumab into standard therapy for locally advanced NPC while removing chemotherapy from the radiation phase. This regimen offers a promising approach to reducing treatment-related toxicities.","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":"143867047","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 : 2025-04-24DOI: 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}
{"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 <em>KMT2C</em> 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 <em>ASPP2</em> 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}
Cancer CellPub Date : 2025-04-17DOI: 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}
Cancer CellPub Date : 2025-04-17DOI: 10.1016/j.ccell.2025.03.032
Živa Moravec, John B.A.G. Haanen, Ton N. Schumacher, Wouter Scheper
{"title":"Learning the language of T cell receptors through large-scale screening","authors":"Živa Moravec, John B.A.G. Haanen, Ton N. Schumacher, Wouter Scheper","doi":"10.1016/j.ccell.2025.03.032","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.032","url":null,"abstract":"T cells perform critical roles in orchestrating immunity in health and disease. However, decoding what individual T cells recognize has long been challenging due to the immense diversity of both T cell receptors (TCRs) and potential antigens. Recent advances in high-throughput TCR screening approaches now provide an opportunity to map the antigen specificity landscape of T cells with unprecedented depth. Here, we outline these recent developments in screening methodologies and discuss how these can help advance our fundamental understanding of T cell-based immunity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"37 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841638","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 : 2025-04-17DOI: 10.1016/j.ccell.2025.03.033
Samson Mathews Samuel, Elizabeth Varghese, Dietrich Büsselberg
{"title":"Complexity of insulin resistance in early-onset colorectal cancer","authors":"Samson Mathews Samuel, Elizabeth Varghese, Dietrich Büsselberg","doi":"10.1016/j.ccell.2025.03.033","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.033","url":null,"abstract":"Early-life exposure to lifestyle-associated metabolic alterations could be a key contributor to early-onset colorectal cancer (EOCRC). Notably, insulin resistance (InsR)-linked hyperinsulinemia, elevated levels of insulin-like growth factors, and chronic inflammation could trigger EOCRC by modulating gene expression/pathways that support carcinogenesis/anti-apoptosis. Here, we discuss how InsR could be the trigger that offsets metabolic homeostasis in young individuals, leading to EOCRC. Furthermore, we emphasize the need for lifestyle interventions, early detection, and targeted therapeutic interventions to mitigate this growing health concern.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"30 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841634","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 : 2025-04-14DOI: 10.1016/j.ccell.2025.03.026
Erik Sahai, Hongxia Wang, Marleen Kok, Catherine J. Wu, Lin Shen, John Carpten, César Serrano, Varun Venkataramani
{"title":"Many paths, one destination: Bridging the gap in cancer care","authors":"Erik Sahai, Hongxia Wang, Marleen Kok, Catherine J. Wu, Lin Shen, John Carpten, César Serrano, Varun Venkataramani","doi":"10.1016/j.ccell.2025.03.026","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.026","url":null,"abstract":"This special issue of <em>Cancer Cell</em> is dedicated to “bridging the gap between foundational cancer biology and clinical oncology.” We asked scientists and clinicians to give us a brief “state of the field,” discussing the integration of new technologies, the importance of patient-centric approaches, the need for innovative clinical trial designs, and how fostering teamwork and inclusive research can help us bridge the gap between cancer research and effective clinical applications.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"137 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827382","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 : 2025-04-14DOI: 10.1016/j.ccell.2025.03.018
Josephine Yates, Eliezer M. Van Allen
{"title":"New horizons at the interface of artificial intelligence and translational cancer research","authors":"Josephine Yates, Eliezer M. Van Allen","doi":"10.1016/j.ccell.2025.03.018","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.018","url":null,"abstract":"Artificial intelligence (AI) is increasingly being utilized in cancer research as a computational strategy for analyzing multiomics datasets. Advances in single-cell and spatial profiling technologies have contributed significantly to our understanding of tumor biology, and AI methodologies are now being applied to accelerate translational efforts, including target discovery, biomarker identification, patient stratification, and therapeutic response prediction. Despite these advancements, the integration of AI into clinical workflows remains limited, presenting both challenges and opportunities. This review discusses AI applications in multiomics analysis and translational oncology, emphasizing their role in advancing biological discoveries and informing clinical decision-making. Key areas of focus include cellular heterogeneity, tumor microenvironment interactions, and AI-aided diagnostics. Challenges such as reproducibility, interpretability of AI models, and clinical integration are explored, with attention to strategies for addressing these hurdles. Together, these developments underscore the potential of AI and multiomics to enhance precision oncology and contribute to advancements in cancer care.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"25 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827141","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 : 2025-04-14DOI: 10.1016/j.ccell.2025.03.024
Steve Mao
{"title":"Bridging the gap: The future of cancer research and clinical oncology in Cancer Cell","authors":"Steve Mao","doi":"10.1016/j.ccell.2025.03.024","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.024","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Over the past five years, <em>Cancer Cell</em> has undergone a transformative evolution, reflecting the increasing multidisciplinary and integrative nature of cancer research. As editor-in-chief, it has been both a privilege and a profound responsibility to guide this journal through a period of significant change and growth, ensuring that it remains at the forefront of cancer research while adapting to the evolving needs of the scientific community. None of this would have been possible without the</section></section>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"26 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827138","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 : 2025-04-14DOI: 10.1016/j.ccell.2025.03.019
Bing Du, Juliang Qin, Boxu Lin, Jiqin Zhang, Dali Li, Mingyao Liu
{"title":"CAR-T therapy in solid tumors","authors":"Bing Du, Juliang Qin, Boxu Lin, Jiqin Zhang, Dali Li, Mingyao Liu","doi":"10.1016/j.ccell.2025.03.019","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.019","url":null,"abstract":"While chimeric antigen receptor (CAR) T cell therapy has shown great success in hematologic malignancies, the effectiveness in solid tumors has been limited by several factors, including antigenic heterogeneity and the immunosuppressive nature of the tumor microenvironment (TME). In this review, we discuss the advancements made in clinical studies and challenges faced by CAR-T therapy for solid tumors. To enhance CAR-T cell efficacy in solid tumors, we explore strategies such as enhancing T cell persistence and cytotoxicity, targeting multiple antigens, and utilizing innovative allogeneic CAR-T cell manufacturing. Additionally, we highlight the potential benefits of combining CAR-T therapies with immune checkpoint inhibitors and other treatment modalities to overcome TME limitations. We remain optimistic about the future of CAR-T cell therapy in solid tumors, emphasizing the need for continued research to refine therapeutic approaches and address the clinical needs of patients with cancer.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"31 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827140","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}