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Engineered Catch Bonds Overcome T-Cell Tolerance in Cancer Therapy. 工程捕获键在癌症治疗中克服t细胞耐受性。
IF 33.3 1区 医学
Cancer discovery Pub Date : 2026-05-01 DOI: 10.1158/2159-8290.CD-RW2026-042
{"title":"Engineered Catch Bonds Overcome T-Cell Tolerance in Cancer Therapy.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-042","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-RW2026-042","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834073","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
Stroma-Driven Neuroplasticity as a Driver of Tumor Progression. 基质驱动的神经可塑性是肿瘤进展的驱动因素。
IF 33.3 1区 医学
Cancer discovery Pub Date : 2026-05-01 DOI: 10.1158/2159-8290.CD-26-0331
Hubert Hondermarck, Luiza Steffens Reinhardt, Chen Chen Jiang
{"title":"Stroma-Driven Neuroplasticity as a Driver of Tumor Progression.","authors":"Hubert Hondermarck, Luiza Steffens Reinhardt, Chen Chen Jiang","doi":"10.1158/2159-8290.CD-26-0331","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-26-0331","url":null,"abstract":"<p><p>In this issue of Cancer Discovery, Nigri and colleagues identify myofibroblastic cancer-associated fibroblasts as drivers of sympathetic nerve recruitment and activation in pancreatic ductal adenocarcinoma. By uncovering a feedforward stromal-sympathetic circuit, the study establishes neuroplasticity as a fibroblast-orchestrated and therapeutically targetable process that is likely applicable across multiple cancer types. See related article by Nigri et al., p. 1014.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"16 5","pages":"834-836"},"PeriodicalIF":33.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811125","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
An Autonomous Cytology Pipeline Enables Clinical-Grade Diagnostics. 自主细胞学管道实现临床级诊断。
IF 33.3 1区 医学
Cancer discovery Pub Date : 2026-05-01 DOI: 10.1158/2159-8290.CD-RW2026-031
{"title":"An Autonomous Cytology Pipeline Enables Clinical-Grade Diagnostics.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-031","DOIUrl":"10.1158/2159-8290.CD-RW2026-031","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580753","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
Autoimmune Response to NMDAR Supports Immunosurveillance of Cancer. 对NMDAR的自身免疫反应支持癌症的免疫监视。
IF 33.3 1区 医学
Cancer discovery Pub Date : 2026-05-01 DOI: 10.1158/2159-8290.CD-RW2026-041
{"title":"Autoimmune Response to NMDAR Supports Immunosurveillance of Cancer.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-041","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-RW2026-041","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834084","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
Checkpoint Breaches: Unexpected Effects of Anti-PD-1 Therapy on the Blood-Brain Barrier. 检查点破坏：抗pd -1治疗对血脑屏障的意外影响。
IF 33.3 1区 医学
Cancer discovery Pub Date : 2026-05-01 DOI: 10.1158/2159-8290.CD-26-0417
Matthia A Karreman, Frank Winkler
{"title":"Checkpoint Breaches: Unexpected Effects of Anti-PD-1 Therapy on the Blood-Brain Barrier.","authors":"Matthia A Karreman, Frank Winkler","doi":"10.1158/2159-8290.CD-26-0417","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-26-0417","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have revolutionized cancer therapy, and their unintended side effects relate largely to inducing autoimmunity; effects on vascular functions have only rarely been observed so far. In this issue of Cancer Discovery, a puzzling finding is reported that has divergent clinical implications: PD-1 inhibitors make cytotoxic T lymphocytes secrete a Wnt pathway suppressor to the blood that opens the blood-brain barrier, both allowing circulating tumor cells to enter the brain and a chemotherapeutic to better reach tumor cells in brain metastases. See related article by Deo et al., p. 976.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"16 5","pages":"831-833"},"PeriodicalIF":33.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811128","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
Epithelial-Fibroblast Crosstalk Supports Early Tumorigenesis. 上皮-成纤维细胞串扰支持早期肿瘤发生。
IF 33.3 1区 医学
Cancer discovery Pub Date : 2026-05-01 DOI: 10.1158/2159-8290.CD-RW2026-035
{"title":"Epithelial-Fibroblast Crosstalk Supports Early Tumorigenesis.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-035","DOIUrl":"10.1158/2159-8290.CD-RW2026-035","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622052","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
Development of CAR T cells Targeting a Surface RNA Binding Protein for the Treatment of Acute Leukemias. 靶向表面RNA结合蛋白的CAR - T细胞治疗急性白血病的研究。
IF 33.3 1区 医学
Cancer discovery Pub Date : 2026-04-30 DOI: 10.1158/2159-8290.CD-25-0920
Takeshi Fujino, Jennifer Lewis, Bingyi Chen, Tamar Y Feinberg, Maxim I Maron, Alexander M Lewis, Charlotte Wishnack, Quinlan Sievers, Satoshi Kaito, Winson Cai, Sarah Yoo, Serena C Mathew, Sydney Souness, Erin Burns, Jasmine Um, Elisa de Stanchina, Qing Chang, Besnik Qeriqi, Kevin Chen, Pu Zhang, Susan DeWolf, Joshua T Weinreb, Renata Mammone, Ileana C Miranda, Robert F Stanley, Maria Adriana Cuibus, Kenyon Weis, Brianna Gipson, Cynthia Castro, Nina Fox, Michael S Lee, Jaime Alvarez-Perez, Daoqi You, Filemon S Dela Cruz, Alyssa D Fronk, Martin Akerman, Andrew L Kung, Omar Abdel-Wahab, Anthony F Daniyan
{"title":"Development of CAR T cells Targeting a Surface RNA Binding Protein for the Treatment of Acute Leukemias.","authors":"Takeshi Fujino, Jennifer Lewis, Bingyi Chen, Tamar Y Feinberg, Maxim I Maron, Alexander M Lewis, Charlotte Wishnack, Quinlan Sievers, Satoshi Kaito, Winson Cai, Sarah Yoo, Serena C Mathew, Sydney Souness, Erin Burns, Jasmine Um, Elisa de Stanchina, Qing Chang, Besnik Qeriqi, Kevin Chen, Pu Zhang, Susan DeWolf, Joshua T Weinreb, Renata Mammone, Ileana C Miranda, Robert F Stanley, Maria Adriana Cuibus, Kenyon Weis, Brianna Gipson, Cynthia Castro, Nina Fox, Michael S Lee, Jaime Alvarez-Perez, Daoqi You, Filemon S Dela Cruz, Alyssa D Fronk, Martin Akerman, Andrew L Kung, Omar Abdel-Wahab, Anthony F Daniyan","doi":"10.1158/2159-8290.CD-25-0920","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-25-0920","url":null,"abstract":"<p><p>Developing chimeric antigen receptor (CAR) T cells for acute myeloid leukemia (AML) has been challenging due to a lack of known AML-associated antigens that spare normal hematopoietic precursor cells. Here we reasoned that donor autoantibodies from AML recipients cured following allogeneic transplant and responsible for graft-versus-leukemia effect could be engineered to create effective CAR-T cells. We generated CAR-T cells against one such antigen - U5 snRNP200, an RNA helicase localized to the AML cell surface and absent from normal hematopoietic precursors. Anti-U5 snRNP200 CAR-T cells were effective in human and syngeneic models of AML as well as B-cell acute lymphoblastic leukemia (B-ALL), a setting where surface U5 snRNP200 is also present. Armoring CAR-T cells with IL-18 led to antigen gain on AML, durable remission, and protection from AML rechallenge. These data thereby identify a CAR-T cell platform which addresses prior limitations in tumor-selectivity and safety for patients with acute leukemias.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":33.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763266","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
Trio of Phase I Studies Investigates Mesothelin-Directed CAR T-Cell Therapies. 三个I期研究探讨间皮素导向CAR - t细胞疗法。
IF 33.3 1区 医学
Cancer discovery Pub Date : 2026-04-30 DOI: 10.1158/2159-8290.CD-NW2026-0049
{"title":"Trio of Phase I Studies Investigates Mesothelin-Directed CAR T-Cell Therapies.","authors":"","doi":"10.1158/2159-8290.CD-NW2026-0049","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-NW2026-0049","url":null,"abstract":"<p><p>At the American Association for Cancer Research Annual Meeting, researchers presented data from three separate phase I studies investigating distinct mesothelin-targeted chimeric antigen receptor T-cell therapies: SynKIR-110, UCMYM802, and M28z1XXPD1DNR.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":33.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763349","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
Toward a New Generation of Glue Degraders. 迈向新一代胶水降解机。
IF 28.2 1区 医学
Cancer discovery Pub Date : 2026-04-29 DOI: 10.1158/2159-8290.cd-nw2026-0048
{"title":"Toward a New Generation of Glue Degraders.","authors":"","doi":"10.1158/2159-8290.cd-nw2026-0048","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-nw2026-0048","url":null,"abstract":"The molecular glue degrader field is growing rapidly, with multiple next-generation candidates in development. Some are targeted against culprit proteins not readily accessible to small-molecule inhibitors, such as ARNT; others aimed at ALK, for instance, may help address the resistance to existing tyrosine kinase inhibitors that inevitably occurs.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"5 1","pages":"OF1"},"PeriodicalIF":28.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754912","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
Diet-induced phospholipid remodeling dictates ferroptosis sensitivity and tumorigenesis in the pancreas. 饮食诱导的磷脂重塑决定了胰腺中铁下垂的敏感性和肿瘤发生。
IF 33.3 1区 医学
Cancer discovery Pub Date : 2026-04-29 DOI: 10.1158/2159-8290.CD-25-0734
Christian Felipe Ruiz, Xiangyu Ge, Rylee McDonnell, Sherry S Agabiti, Daniel C McQuaid, Andy Tang, Meera Kharwa, Jennifer Goodell, Rocio Del M Saavedra-Pena, Allison Wing, Guangtao Li, Natasha Pinto Medici, Marie E Robert, Rohan R Varshney, Michael C Rudolph, Fred S Gorelick, John Wysolmerski, Daniel Canals, John D Haley, Matthew S Rodeheffer, Mandar Deepak Muzumdar
{"title":"Diet-induced phospholipid remodeling dictates ferroptosis sensitivity and tumorigenesis in the pancreas.","authors":"Christian Felipe Ruiz, Xiangyu Ge, Rylee McDonnell, Sherry S Agabiti, Daniel C McQuaid, Andy Tang, Meera Kharwa, Jennifer Goodell, Rocio Del M Saavedra-Pena, Allison Wing, Guangtao Li, Natasha Pinto Medici, Marie E Robert, Rohan R Varshney, Michael C Rudolph, Fred S Gorelick, John Wysolmerski, Daniel Canals, John D Haley, Matthew S Rodeheffer, Mandar Deepak Muzumdar","doi":"10.1158/2159-8290.CD-25-0734","DOIUrl":"10.1158/2159-8290.CD-25-0734","url":null,"abstract":"<p><p>High-fat diet (HFD) intake has been linked to an increased risk of pancreatic ductal adenocarcinoma (PDAC), a lethal and therapy-resistant cancer. However, whether and how specific dietary fats drive cancer development remains unresolved. Leveraging an oncogenic Kras-driven mouse model that closely mimics human PDAC progression, we screened a dozen isocaloric HFDs differing solely in fat source and representing the diversity of human fat consumption. Unexpectedly, diets rich in oleic acid - a monounsaturated fatty acid (MUFA) typically associated with good health - markedly enhanced tumorigenesis. Conversely, diets high in polyunsaturated fatty acids (PUFAs) suppressed tumor progression. Relative dietary fatty acid saturation levels (PUFA/MUFA) governed pancreatic membrane phospholipid composition, lipid peroxidation, and ferroptosis sensitivity in mice, concordant with circulating PUFA/MUFA levels being linked to altered PDAC risk in humans. These findings directly implicate dietary unsaturated fatty acids in controlling ferroptosis susceptibility and tumorigenesis, supporting potential \"precision nutrition\" strategies for PDAC prevention.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":33.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763316","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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