Cancer discovery最新文献

{"title":"How a Rare Inherited Lung Cancer Mutation Took Root in Appalachia","authors":"","doi":"10.1158/2159-8290.cd-nw2026-0089","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-nw2026-0089","url":null,"abstract":"A rare inherited EGFR mutation took root in Southern Appalachia after being carried to the United States by European settlers in the 1700s. Mapping the distribution of this germline EGFRT790M variant could help clinicians identify people at elevated risk of lung cancer and target them for genetic testing and closer surveillance.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"82 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148985103","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":"Targeting BLVRB Overcomes Immunosuppression and Potentiates Immunotherapy in Monocytic Acute Myeloid Leukemia.","authors":"Zhuomao Mo, Jianyu Wang, Yin Zhao, Xinghua Liang, Lina Liu, Jun Liu, Kaiting Wang, Lulu Qin, Miaomiao Su, Hezhou Guo, Yuxuan Chen, Xiaoyang Sun, Ruiting Yan, Jie Sun, Yongxian Hu, He Huang, Shanshan Pei, Dongrui Wang","doi":"10.1158/2159-8290.CD-26-0447","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-26-0447","url":null,"abstract":"<p><p>Acute Myeloid Leukemia (AML) is characterized by significant immunosuppression, limiting the efficacy of immunotherapy. Monocytic AML presents unique immunosuppressive features and constitutes a challenging subtype necessitating focused investigation. Using single-cell multi-omics analyses of primary AML samples, we revealed the immunosuppression landscape of monocytic AML and identified BLVRB as a marker of immunosuppressive monocytic AML cells. BLVRB depletion downregulated immune-modulatory gene expression and sensitized AML cells to T cell cytotoxicity, resulting in improved therapeutic efficacy in cell line and patient-derived xenograft models. Mechanistically, BLVRB signals through the transcription factor MAFB to masterfully promote the expression of various immunosuppression-associated genes, resulting in inhibitory effect against anti-AML T cells. We further demonstrated that the small molecule Tamibarotene targets BLVRB, enhancing the efficacy of both CAR-T and anti-PD-1 antibody therapies in AML. These findings elucidate the critical mechanism regulating immunosuppression in monocytic AML and identify BLVRB as a therapeutic target for improving AML immunotherapy.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":29.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966483","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":"O-mannosylation and protein maturation checkpoints represent therapeutic opportunities in BRAF fusion protein oncogenesis.","authors":"Anna Borgenvik, Sean A Misek, Daniel Christen, Gloria Kyrila, Alexander Zhang, Sarah Reel, Michelle Boisvert, Kelly Y Cai, Anna Kovarzin, Hongyu Li, Kevin N Zhou, Elizabeth M Gonzalez, Sara C Buch-Larsen, Ivo A Hendriks, Jesper V Olsen, Corina Anastasaki, Enquan Xu, Amy Goodale, Lorena Lazo de la Vega, Timothy J Ragnoni, Zohra Kalani, Nicole S Persky, Tanaz Abid, Esteban A Miglietta, Sergey Y Vakhrushev, Michael Stumpe, Jacquelyn S Jones, Seth Malinowski, Lobna A Elsadek, Julie Parikh, Alexandra L Condurat, Aaron Fultineer, Seung Hyun Choi, Merve Ozdemir, Zachary Eisenbies, Joohee Lee, Dana Novikov, Sher Bahadur, April A Apfelbaum, Jenna Robinson, Louise M Clark, Noah Schulman, Gianluca Lopez, Daniela Kocher, Carolina Ortiz-Cordero, Kira Tang, Antonio Maldera, Daniel P Bondeson, Jason J Kwon, Mounica Vallurupalli, Hyesung Jeon, Sangita Pal, Sandra Jacobs, Todd R Golub, William C Hahn, Frederik De Smet, Romain Sigaud, Eric S Fischer, Jesse S Boehm, Jörn Dengjel, Henrik Clausen, Nada Jabado, Till Milde, Anne E Carpenter, David H Gutmann, Beth A Cimini, Keith L Ligon, Katherine A Janeway, Michael J Eck, Brittany C Parker Kerrigan, David E Root, David T W Jones, Tanaz Sharifnia, Timothy N Phoenix, Rameen Beroukhim, Hiren J Joshi, Tilman Brummer, Adnan Halim, Pratiti Bandopadhayay","doi":"10.1158/2159-8290.CD-25-1114","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-25-1114","url":null,"abstract":"<p><p>Fusions between protein-coding genes are common oncogenic drivers, typically pairing a proto-oncogene with a partner that does not independently drive cancer. In all therapeutically actionable fusions, the proto-oncogene is the drug target, the contributions to oncogenicity of the fusion partner have largely been ignored. We studied the role of BRAF fusion partners and found that they are necessary for transformation. In the setting of KIAA1549::BRAF, the most common fusion protein across brain tumors, we found that KIAA1549 is necessary for oncogenicity of KIAA1549::BRAF and engenders a striking and specific dependency on the protein O-mannosyltransferase complex (POMT1/2). Specifically, we show that genetic silencing or pharmacologic inhibition of POMT1/2 reverses fusion-induced transformation, thereby representing a novel and MAPK-independent therapeutic target. Furthermore, POMT1/2 is required to glycosylate and enable maturation of the K::B fusion protein. These findings represent a proof-of-concept for targeting the partners in oncogenic fusions as a potential cancer therapeutic strategy.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":29.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910997","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":"Nucleoporins in Cancer: Functional Roles and Therapeutic Opportunities.","authors":"Perumalraja Kirthika, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Josep Domingo-Domenech, Veronica Rodriguez-Bravo","doi":"10.1158/2159-8290.CD-26-0347","DOIUrl":"10.1158/2159-8290.CD-26-0347","url":null,"abstract":"<p><p>The nuclear pore complex (NPC) and its building-block proteins, nucleoporins (NUP), play fundamental roles in maintaining cellular fitness by regulating nucleocytoplasmic transport, chromatin and transcriptional activity, and genome stability. These core biological processes are critical for cancer cells, and thus, tumor-driven co-option of NUP-regulated functions has emerged as an important mechanism contributing to the pathogenesis of multiple malignancies. This review discusses how NUP dysregulation mechanistically contributes to tumor initiation and progression and how these insights open opportunities for innovative anticancer therapies, including using clinical-grade molecular glues that induce selective NUP degradation and pharmacologically inhibiting NPC-regulated epigenomic/transcriptomic signaling and nucleocytoplasmic transport.</p><p><strong>Significance: </strong>Recent studies demonstrate that NUPs play fundamental roles in cancer pathogenesis by dysregulating key NPC functions and driving tumorigenesis and disease progression. NUPs and NPC-regulated mechanisms can be pharmacologically targeted, providing a strong rationale for developing much-needed innovative therapeutic strategies to combat cancer.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1-OF12"},"PeriodicalIF":29.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918536","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":"Q&A: Keith Flaherty on Advances in Cancer Research","authors":"","doi":"10.1158/2159-8290.cd-nw2026-0087","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-nw2026-0087","url":null,"abstract":": Keith T. Flaherty, MD, who began a 1-year term as president of the American Association for Cancer Research in April 2026, spoke with Cancer Discovery’s Suzanne Rose about his work, what he sees as the most exciting advances in cancer research, and his vision for the future.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"59 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148902027","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":"New Studies Showcase Capabilities of Organoids.","authors":"","doi":"10.1158/2159-8290.CD-NW2026-0086","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-NW2026-0086","url":null,"abstract":"<p><p>Three recent papers show the potential benefits of several hundred new organoids, spheroids, and other cancer models. One study demonstrates that more than 600 of the models mirror their parent tumors. A second study uses organoids to uncover new cancer dependencies, or essential genes, in 147 organoids from 10 cancer types. The third study also identifies new cancer dependencies and shows that organoids from individual patients might lead to new treatment choices.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":29.5,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886612","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":"Pan-RAS Inhibitor Shows Activity in Advanced Lung Cancer","authors":"","doi":"10.1158/2159-8290.cd-nw2026-0085","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-nw2026-0085","url":null,"abstract":": The first-in-class pan-RAS inhibitor daraxonrasib shrank tumors in more than 30% of patients with previously treated RAS-mutant non–small cell lung cancer. The findings build on results that recently earned approval for the drug against pancreatic cancer and support an ongoing phase III trial in lung cancer.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"16 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877307","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":"Functionally active lymphoid aggregates correlate with improved prognosis in brain metastases.","authors":"Noor E Nader, Alexandra R Glathar, Elaine V Byrnes, Marion Joy, Tengziyi Ge, Andrew Elliott, Ryan Jaehne, Caroline J Layding, Curtis Mamoru Tatsuoka, Gabriel Sica, Rajesh Acharya, Riyue Bao, Anthony R Cillo, Aron Y Joon, Swaminathan Kumar, Rami B Yanes, Xiancheng Wu, Luisa M Solis Soto, Claudio A Arrechedera, Auriole Tamegnon, Beatriz Sanchez-Espiridion, Hussein A Tawbi, Elizabeth M Burton, Michael A Davies, Thomas M Pearce, Timothy F Burns, Laura P Stabile, Xiaoran Zhang, Tullia C Bruno","doi":"10.1158/2159-8290.CD-25-0731","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-25-0731","url":null,"abstract":"<p><p>B cells and their cellular neighborhoods, i.e., lymphoid aggregates (LAs) and tertiary lymphoid structures (TLS), have not been extensively studied in melanoma brain metastases (BM) or lung adenocarcinoma (LUAD) BM, despite their prognostic value and role in immunotherapeutic responses. In this study, we evaluated the prognostic benefit and heterogeneity of B cell infiltration and LA formation in more than 200 patients with melanoma-BM or LUAD-BM. We found that LAs were associated with increased intratumoral CD8+T cells in melanoma-BM compared with LUAD-BM. Moreover, the presence of LAs was associated with an increased survival benefit in patients with melanoma-BM but not in those with LUAD-BM. Despite lacking canonical TLS hallmarks, LAs in BM contained proliferating B and T cells with the potential for effector function. Our work has solidified the need for the mechanistic investigation of intracranial B cells and the immune neighborhoods in which they reside.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":29.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872811","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":"First-Line HER2 ADC and Anti-PD-1 Plus Chemo Shows Efficacy in Gastric Cancer.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-070","DOIUrl":"10.1158/2159-8290.CD-RW2026-070","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":29.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757535","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":"Ketogenic Diet Promotes Intestinal Tumorigenesis Via Lipid Oxidation.","authors":"","doi":"10.1158/2159-8290.CD-RW2026-076","DOIUrl":"10.1158/2159-8290.CD-RW2026-076","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"OF1"},"PeriodicalIF":29.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817508","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}