{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nussbaum DP"],"funding":["U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)","American Cancer Society","Duke University","U.S. Department of Health & Human Services | NIH | National Cancer Institute","American Cancer Society (American Cancer Society, Inc.)","U.S. Department of Defense","U.S. Department of Defense (United States Department of Defense)","NCI NIH HHS","NIGMS NIH HHS","Duke University (Duke)"],"pagination":["124"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11143207"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(1)"],"pubmed_abstract":["Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treatment responses. Here, we developed multiple models of acquired resistance to dual-mechanism ERK/MAPK inhibitors across KRAS-mutant pancreatic, colorectal, and lung cancers, and then probed the long-term events enabling survival against this class of drugs. These studies revealed that resistance emerges secondary to large-scale transcriptional adaptations that are diverse and cell line-specific. Transcriptional reprogramming extends beyond the well-established early response, and instead represents a dynamic, evolved process that is refine"],"journal":["NPJ precision oncology"],"pubmed_title":["Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers."],"pmcid":["PMC11143207"],"funding_grant_id":["R01 CA207083","P01 CA203657","W81XWH2110362","K22 CA276632","P30 CA008748","F32CA180569","R01 CA263593","PF 18-061","5F32CA268527","F32 CA268527","R01 CA175747","R01CA207083","U01 CA199235","R01CA263593","R35 GM139550","R35 CA232113","P01CA203657","U01CA199235","N/A (Start-Up Funds)","R01CA175747","F32 CA180569","R37 CA248289","R35CA232113"],"pubmed_authors":["Martz CA","Nussbaum DP","Pierobon M","Levandowski CB","Wu C","Waters AM","Cerda-Smith CG","Rutter JC","Kantrowitz DE","McCall SJ","Reddy TE","Liu A","Wood KC","Joshua Smith J","Stewart AE","Der CJ","Barrera A","Petricoin EF","Cakir M","Taatjes DJ"],"additional_accession":[]},"is_claimable":false,"name":"Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers.","description":"Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treatment responses. Here, we developed multiple models of acquired resistance to dual-mechanism ERK/MAPK inhibitors across KRAS-mutant pancreatic, colorectal, and lung cancers, and then probed the long-term events enabling survival against this class of drugs. These studies revealed that resistance emerges secondary to large-scale transcriptional adaptations that are diverse and cell line-specific. Transcriptional reprogramming extends beyond the well-established early response, and instead represents a dynamic, evolved process that is refine","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-03T03:56:18.22Z","creation":"2026-04-24T03:09:25.622Z"},"accession":"S-EPMC11143207","cross_references":{"pubmed":["38822082"],"doi":["10.1038/s41698-024-00615-9"]}}