Dasatinib resensitizes BRAF/MEK inhibitor efficacy in patient-derived xenografts from patients with progression on BRAF/MEK inhibitor treatment

iScience 2026 Open access

Read full text
Authors: Vito W. Rebecca, Min Xiao, Andrew V. Kossenkov, Tetiana Godok, Gregory Schuyler Brown, Dylan F. Fingerman, Gretchen Marie Alicea, Meihan Wei, Hongkai Ji, Marie Elena Portuallo, Jeremy Bravo, Vissy M. Elad
+15 more Yeqing Chen, Eneda Toska, Mitchell E. Fane, Kasey L. Couts, Jessie Villanueva, Katherine Nathanson, Keerthana M. Arun, Govind Warrier, Xiangfan Yin, Jianyi Ding, Qin Liu, Yogesh Goyal, Y.N. Vashisht Gopal, Michael A. Davies, Meenhard Herlyn
DOI: 10.1016/j.isci.2026.114669
Cited by: 0
References: 48

Abstract

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.

Fields of Study & Subjects

Melanoma and MAPK Pathways Protein Tyrosine Phosphatases Colorectal Cancer Treatments and Studies

Publication details

Journal / source
iScience
Volume
29
Issue
2
Pages
114669–114669
Publication date
13 January 2026
Language
EN