Resistance to kinase inhibition through shortened target engagement

Mol Cell Oncol. 2022 Jan 22;9(1):2029999. doi: 10.1080/23723556.2022.2029999. eCollection 2022.

Abstract

Imatinib, a selective inhibitor of the breakpoint cluster region (BCR)-ABL kinase, is the poster child for targeted cancer therapeutics. However, its efficacy is limited by resistance mutations. Using a quantitative bioluminescence resonance energy transfer assay in living cells, we identified ABL kinase mutations that could cause imatinib resistance by altering drug residence time.