{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["29(2)"],"submitter":["Rebecca VW"],"pubmed_abstract":["Although BRAF/MEK inhibitor (BRAFi/MEKi) therapy initially shows high efficacy in patients with <i>BRAF</i> <sup>V600 E/K</sup> cutaneous melanoma, resistance develops in over 75% of cases. We tested robustness of the umbrella trial strategy in this population by analyzing relationships between genomic status of a gene and associated downstream consequences at the protein level. The results revealed weak relationships among mutations, copy-number amplification, and protein expression and activation. An <i>in vivo</i> compound repurposing screen using 11 clinically relevant agents from an NCI-portfolio with pan-RTK, non-RTK, and/or PI3K-mTOR specificity identified dasatinib as most capable of restoring sensitivity to BRAFi/MEKi in patient-derived xenograft (PDX) models originating from tumors that had progressed on BRAFi ± MEKi. High baseline expression of BRAFi/MEKi resistance-associated proteins (e.g., AXL, YAP, HSP70, and phospho-AKT) was predictive of the response to BRAFi/MEKi + dasatinib combination therapy. These findings suggest that adding dasatinib may help overcome resistance and restore anti-tumor activity in patients with BRAFi/MEKi-refractory cutaneous melanoma."],"journal":["iScience"],"pagination":["114669"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907876"],"repository":["biostudies-literature"],"pubmed_title":["Dasatinib resensitizes BRAF/MEK inhibitor efficacy in patient-derived xenografts from patients with progression on BRAF/MEK inhibitor treatment."],"pmcid":["PMC12907876"],"pubmed_authors":["Herlyn M","Rebecca VW","Liu Q","Warrier G","Brown GS","Gopal YNV","Ding J","Goyal Y","Toska E","Fane ME","Wei M","Godok T","Kossenkov A","Couts KL","Chen Y","Alicea GM","Fingerman D","Yin X","Ji H","Bravo J","Villanueva J","Nathanson K","Xiao M","Arun KM","Davies MA","Portuallo M","Elad V"],"additional_accession":[]},"is_claimable":false,"name":"Dasatinib resensitizes BRAF/MEK inhibitor efficacy in patient-derived xenografts from patients with progression on BRAF/MEK inhibitor treatment.","description":"Although BRAF/MEK inhibitor (BRAFi/MEKi) therapy initially shows high efficacy in patients with <i>BRAF</i> <sup>V600 E/K</sup> cutaneous melanoma, resistance develops in over 75% of cases. We tested robustness of the umbrella trial strategy in this population by analyzing relationships between genomic status of a gene and associated downstream consequences at the protein level. The results revealed weak relationships among mutations, copy-number amplification, and protein expression and activation. An <i>in vivo</i> compound repurposing screen using 11 clinically relevant agents from an NCI-portfolio with pan-RTK, non-RTK, and/or PI3K-mTOR specificity identified dasatinib as most capable of restoring sensitivity to BRAFi/MEKi in patient-derived xenograft (PDX) models originating from tumors that had progressed on BRAFi ± MEKi. High baseline expression of BRAFi/MEKi resistance-associated proteins (e.g., AXL, YAP, HSP70, and phospho-AKT) was predictive of the response to BRAFi/MEKi + dasatinib combination therapy. These findings suggest that adding dasatinib may help overcome resistance and restore anti-tumor activity in patients with BRAFi/MEKi-refractory cutaneous melanoma.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-09T13:24:19.495Z","creation":"2026-07-09T13:10:13.981Z"},"accession":"S-EPMC12907876","cross_references":{"pubmed":["41704766"],"doi":["10.1016/j.isci.2026.114669"]}}