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pH-Responsive Membranolytic Peptide Enhances Tumor Immunogenicity. ph反应性膜溶肽增强肿瘤免疫原性。
IF 29.5 1区 医学
Cancer discovery Pub Date : 2026-10-01 DOI: 10.1158/2159-8290.CD-RW2026-082
{"title":"pH-Responsive Membranolytic Peptide Enhances Tumor Immunogenicity.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-082","DOIUrl":"10.1158/2159-8290.CD-RW2026-082","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":29.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963103","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}
引用次数: 0
Correction: EZH2 -Deficient T-Cell Acute Lymphoblastic Leukemia is Sensitized to CHK1 Inhibition Through Enhanced Replication Stress 更正：EZH2缺陷t细胞急性淋巴细胞白血病通过增强复制应激对CHK1抑制敏感
IF 28.2 1区 医学
Cancer discovery Pub Date : 2026-10-01 DOI: 10.1158/2159-8290.cd-26-1718
Theresa E. León,Tanya Rapoz-D’Silva,Cosetta Bertoli,Sunniyat Rahman,Michael Magnussen,Brian Philip,Nadine Farah,Simon E. Richardson,Sara Ahrabi,José Afonso Guerra-Assunção,Rajeev Gupta,Elisabeth P. Nacheva,Stephen Henderson,Javier Herrero,David C. Linch,Robertus A.M. de Bruin,Marc R. Mansour
{"title":"Correction:\u0000 EZH2\u0000 -Deficient T-Cell Acute Lymphoblastic Leukemia is Sensitized to CHK1 Inhibition Through Enhanced Replication Stress","authors":"Theresa E. León,Tanya Rapoz-D’Silva,Cosetta Bertoli,Sunniyat Rahman,Michael Magnussen,Brian Philip,Nadine Farah,Simon E. Richardson,Sara Ahrabi,José Afonso Guerra-Assunção,Rajeev Gupta,Elisabeth P. Nacheva,Stephen Henderson,Javier Herrero,David C. Linch,Robertus A.M. de Bruin,Marc R. Mansour","doi":"10.1158/2159-8290.cd-26-1718","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-26-1718","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"15 1","pages":"2197-2197"},"PeriodicalIF":28.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088316","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}
引用次数: 0
Studying Ferroptosis in the Tumor Microenvironment 肿瘤微环境下铁下垂的研究
IF 28.2 1区 医学
Cancer discovery Pub Date : 2026-10-01 DOI: 10.1158/2159-8290.cd-26-0232
Marie Sabatier, Jessalyn M. Ubellacker
{"title":"Studying Ferroptosis in the Tumor Microenvironment","authors":"Marie Sabatier, Jessalyn M. Ubellacker","doi":"10.1158/2159-8290.cd-26-0232","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-26-0232","url":null,"abstract":"Summary: Despite strong preclinical evidence, ferroptosis-based strategies have not yet translated into the clinic, in part due to the disconnect between conventional in vitro models and the complex tumor microenvironment. In this commentary, we consider ferroptosis as a microenvironmentally regulated process and call for multidisciplinary approaches that bridge foundational ferroptosis biology with clinically actionable interventions grounded in the context of the tumor microenvironment.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"6 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086346","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}
引用次数: 0
Quality over Quantity: Dietary Fatty Acid Composition Shapes Pancreatic Tumorigenesis 质重于量：膳食脂肪酸组成影响胰腺肿瘤的发生
IF 28.2 1区 医学
Cancer discovery Pub Date : 2026-10-01 DOI: 10.1158/2159-8290.cd-26-1528
Yu-Jin Jeong, Evan C. Lien
{"title":"Quality over Quantity: Dietary Fatty Acid Composition Shapes Pancreatic Tumorigenesis","authors":"Yu-Jin Jeong, Evan C. Lien","doi":"10.1158/2159-8290.cd-26-1528","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-26-1528","url":null,"abstract":"Summary: Obesity and high dietary fat consumption are associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC), and Ruiz and colleagues show that in addition to total fat consumption, distinct types of dietary fat contribute differently to tumor initiation in murine PDAC models. Diets rich in monounsaturated fatty acids enhance tumor progression, whereas dietary polyunsaturated fatty acids suppress tumorigenesis by increasing pancreatic cell susceptibility to lipid peroxidation and ferroptosis. See related article by Ruiz et al., p. 2108","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"11 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086347","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}
引用次数: 0
When Neutrophils Do Not Die: Senescence as a New Axis of Tumor Immunosuppression 当中性粒细胞不死亡：衰老作为肿瘤免疫抑制的新轴
IF 28.2 1区 医学
Cancer discovery Pub Date : 2026-10-01 DOI: 10.1158/2159-8290.cd-26-1529
Lucie Droin, Hannah Garner
{"title":"When Neutrophils Do Not Die: Senescence as a New Axis of Tumor Immunosuppression","authors":"Lucie Droin, Hannah Garner","doi":"10.1158/2159-8290.cd-26-1529","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-26-1529","url":null,"abstract":"Summary: In this issue of Cancer Discovery, Chen and colleagues leverage single-cell RNA sequencing of neutrophils in the tumor microenvironment of colorectal cancer liver metastases to characterize neutrophil heterogeneity within the metastatic immune landscape. They show that the glucose-deprived metastatic microenvironment drives BHLHE40 upregulation in neutrophils, inducing a senescent tumor-associated neutrophil (TAN) population, TAN1, that actively promotes angiogenesis and excludes CD8+ T cells from the tumor, thereby supporting tumor growth and survival. See related article by Chen et al., p. 2130","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"298 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086389","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}
引用次数: 0
ctDNA Profiling Identifies Daraxonrasib Resistance Mechanisms. ctDNA分析鉴定Daraxonrasib耐药机制
IF 29.5 1区 医学
Cancer discovery Pub Date : 2026-10-01 DOI: 10.1158/2159-8290.CD-RW2026-083
{"title":"ctDNA Profiling Identifies Daraxonrasib Resistance Mechanisms.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-083","DOIUrl":"10.1158/2159-8290.CD-RW2026-083","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":29.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976020","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}
引用次数: 0
Rb Activates Pro-Proliferative Estrogen-Responsive Genes in Breast Cancer. Rb在乳腺癌中激活促增殖雌激素反应基因。
IF 29.5 1区 医学
Cancer discovery Pub Date : 2026-10-01 DOI: 10.1158/2159-8290.CD-RW2026-084
{"title":"Rb Activates Pro-Proliferative Estrogen-Responsive Genes in Breast Cancer.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-084","DOIUrl":"10.1158/2159-8290.CD-RW2026-084","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":29.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988135","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}
引用次数: 0
Caloric Intake Impacts Somatic Mutation Burden Across Mouse Tissues. 热量摄入影响小鼠组织的体细胞突变负担。
IF 29.5 1区 医学
Cancer discovery Pub Date : 2026-09-30 DOI: 10.1158/2159-8290.CD-RW2026-087
{"title":"Caloric Intake Impacts Somatic Mutation Burden Across Mouse Tissues.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-087","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-RW2026-087","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":29.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079896","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}
引用次数: 0
Cancer AI Moves Toward Foundation Model Combos 癌症AI转向基础模型连击
IF 28.2 1区 医学
Cancer discovery Pub Date : 2026-09-29 DOI: 10.1158/2159-8290.cd-nw2026-0093
{"title":"Cancer AI Moves Toward Foundation Model Combos","authors":"","doi":"10.1158/2159-8290.cd-nw2026-0093","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-nw2026-0093","url":null,"abstract":": Foundation models are transforming cancer AI, but no single model consistently excels across every task. Researchers are increasingly combining models to improve performance and robustness, from interpreting pathology slides to selecting drugs for individual tumors.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"10 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070932","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}
引用次数: 0
Spatial modulation of RAF by RAF/MEK glue enables full-dose combination with pan-RAF inhibitor and potent RAS-mutant tumor-selective MAPK and growth inhibition. 通过RAF/MEK胶对RAF进行空间调节，实现了与泛RAF抑制剂和强效ras突变肿瘤选择性MAPK的全剂量联合和生长抑制。
IF 29.5 1区 医学
Cancer discovery Pub Date : 2026-09-29 DOI: 10.1158/2159-8290.CD-25-1596
Ana Orive-Ramos, Bijaya Gaire, Christos Adamopoulos, Beau Baars, Mathieu Desaunay, Ziyue Kou, Evangelia Matenoglou, Silvia Coma, Nayeli Gutiérrez Trejo, Kevin Mohammed, Stuart A Aaronson, Jian Jin, Tiphaine C Martin, Ernesto Guccione, Evripidis Gavathiotis, Jonathan A Pachter, Poulikos I Poulikakos
{"title":"Spatial modulation of RAF by RAF/MEK glue enables full-dose combination with pan-RAF inhibitor and potent RAS-mutant tumor-selective MAPK and growth inhibition.","authors":"Ana Orive-Ramos, Bijaya Gaire, Christos Adamopoulos, Beau Baars, Mathieu Desaunay, Ziyue Kou, Evangelia Matenoglou, Silvia Coma, Nayeli Gutiérrez Trejo, Kevin Mohammed, Stuart A Aaronson, Jian Jin, Tiphaine C Martin, Ernesto Guccione, Evripidis Gavathiotis, Jonathan A Pachter, Poulikos I Poulikakos","doi":"10.1158/2159-8290.CD-25-1596","DOIUrl":"10.1158/2159-8290.CD-25-1596","url":null,"abstract":"<p><p>Effective MAPK-targeted therapies require greater pathway inhibition in tumors than in normal tissues. Although pan-RAF inhibitors have demonstrated activity in RAS-mutant cancers, combinations with MEK inhibitors require dose reductions because of toxicity, limiting clinical benefit. Here, we show that this toxicity results from MEK inhibitor-mediated feedback relief, which promotes RAF activation and enhances pan-RAF inhibitor binding in normal cells. We identify a distinct mechanism of RAF inhibition by RAF/MEK glues: by stabilizing RAF-MEK complexes, these compounds trap RAF in the cytosol, preventing membrane recruitment required for RAF activation. This spatial modulation mechanism preserves tumor-selective MAPK inhibition and enables full-dose combination therapy with pan-RAF inhibitors. This therapeutic strategy produced robust tumor regressions in multiple RAS-mutant tumor models, including models refractory to current RAS/MAPK-targeting therapies. Our findings underscore drug-induced proximity as a strategy to achieve tumor selectivity and support the clinical development of RAF/MEK glue plus pan-RAF inhibitor combinations for RAS-mutant tumors.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":29.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079860","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}
引用次数: 0
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