Cancer discovery最新文献

{"title":"Extracellular Inversion of Src Creates a Targetable Cancer Surface Antigen.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-047","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-RW2026-047","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834118","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":"Androgens Delay Hindbrain Differentiation and Drive PFA Ependymoma.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-046","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-RW2026-046","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834146","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":"Reactivation of Fetal Morphogenesis Signals Predicts Breast Cancer Metastasis.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-044","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-RW2026-044","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834191","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":"Proteasome-Heme Axis Links Mitochondrial Stress to T-Cell Exhaustion.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-043","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-RW2026-043","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834059","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":"The evolution of polyclonal competition in aging hematopoiesis.","authors":"Nathaniel V Mon Père, Francesco Terenzi, Benjamin Werner","doi":"10.1158/2159-8290.CD-25-0990","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-25-0990","url":null,"abstract":"<p><p>Clonal hematopoiesis (CH) - the expansion of genetic variants in blood - is a prime example of somatic evolution. Although it often precedes malignant transformation, many aspects of this process remain unknown. We show that a model of polyclonal competition, in which selectively-advantaged clones continually appear and compete, explains observed CH dynamics throughout human life. We quantify the fitness distribution and occurrence rate of clonal expansions using either variant trajectories or HSC genetic heterogeneity. Inferences on both data converge. Approximately three fit clones enter the HSC pool per year, yet rarely more than five achieve >1.5% frequency throughout life. The fittest clones emerge predominantly later in life in accordance with a multistep evolutionary process. DNMT3A-variants were enriched for single-hit clones, whereas TET2, ASXL1, JAK2, SF3B1, and SRSF2 showed enrichment for multi-hit evolution. These findings suggest precursors of hematological malignancies are identifiable prior to transformation and may facilitate early intervention strategies.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":33.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834243","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":"Synthetic Super-Enhancers Allow for Precise Antitumor Therapy.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-045","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-RW2026-045","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834218","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":"Cancer Throughlines: 40 Years After Chernobyl Disaster, Research on Cancer Impact Carries On.","authors":"","doi":"10.1158/2159-8290.CD-NW2026-0045","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-NW2026-0045","url":null,"abstract":"<p><p>On April 26, 1986, Reactor Number 4 at the Chernobyl Nuclear Power Plant exploded, releasing massive amounts of radioactive material into the atmosphere. Exposed children contracted papillary thyroid carcinoma at elevated rates, and on the eve of the 40-year anniversary, many studies are now focused on the transgenerational health effects of the disaster.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834144","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":"Robust Findings for HER2 TKI in NSCLC.","authors":"","doi":"10.1158/2159-8290.CD-NW2026-0051","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-NW2026-0051","url":null,"abstract":"<p><p>Among 74 patients newly diagnosed with HER2-mutant NSCLC who received a daily dose of zongertinib, the objective response rate was 76% and the median progression-free survival was 14.4 months. That bests chemotherapy, to which about 30% of patients typically respond for less than 7 months.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811188","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":"Myofibroblasts Induce Neuroplasticity to Promote Pancreatic Inflammation and Cancer Progression.","authors":"Jérémy Nigri, Wenjun Lan, Melanie L Fung, Charlotte Kayser, Astrid Deschênes, Juliene Hinds, Sanjeev Kaushalya, Sara A Pawlak, Jennifer S Thalappillil, Sandeep Nadella, Marc Hilmi, Wungki Park, Rajya Kappagantula, Youngkyu Park, Zhen Zhao, Jonathan Preall, Christine A Iacobuzio-Donahue, Kevin J Tracey, Jeremy C Borniger, David A Tuveson","doi":"10.1158/2159-8290.CD-25-1337","DOIUrl":"10.1158/2159-8290.CD-25-1337","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) co-opts the peripheral nervous system through nerve hypertrophy, axonogenesis, and perineural invasion, and these processes correlate with patient morbidity and mortality. Prior work has shown that autonomic nerves directly modulate neoplastic cells in PDAC, but whether cancer-associated fibroblasts (CAF) participate in neural remodeling is unknown. Using thick tissue sections, we identified dense neo-innervation near myofibroblastic CAFs (myCAF) in preinvasive pancreatic intraepithelial neoplasms. Mechanistically, TGFβ produced during inflammation and neoplasia triggers myofibroblast formation, and myCAFs produce axon guidance molecules that recruit sympathetic nerves. Norepinephrine released by sympathetic nerves activates myofibroblast cultures in vitro, and sympathetic nerve depletion impairs stromal activation and PDAC growth in vivo. A chemogenetic model confirmed that fibroblast-specific α1-adrenergic signaling exacerbated pancreatic inflammation and neoplasia. Therefore, beyond direct epithelial effects, sympathetic nerves promote pancreatitis and PDAC by co-opting myofibroblasts and myCAFs as disease amplifiers, highlighting CAF subtype-specific stromal interactions as putative therapeutic targets.</p><p><strong>Significance: </strong>Pathology-associated myofibroblasts orchestrate bidirectional cross-talk with sympathetic neurons, secreting axon guidance molecules to promote nerve infiltration in inflamed and neoplastic pancreatic tissues. Specifically, α1-adrenoreceptor activation in fibroblasts acts as a molecular switch that amplifies pancreatitis severity and accelerates tumor growth, revealing new paracrine and juxtacrine interactions for further therapeutic development. See related commentary by Hondermarck et al., p.834.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"1014-1034"},"PeriodicalIF":33.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141015","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}

{"title":"A New Class of Molecular Glues: Double Allostery Restores KEAP1 Control of NRF2.","authors":"Jordi C J Hintzen, George M Burslem","doi":"10.1158/2159-8290.CD-26-0342","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-26-0342","url":null,"abstract":"<p><p>Roy and colleagues describe VVD-065, a covalent allosteric molecular glue that binds KEAP1 at Cys151 to enhance KEAP1-CUL3 assembly, restore NRF2 ubiquitination and degradation, and selectively suppress NRF2-driven tumors by reactivating endogenous E3 ligase function. See related article by Roy et al., p. 953.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"16 5","pages":"829-830"},"PeriodicalIF":33.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811122","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}