Mechanisms of resistance to BCR-ABL and other kinase inhibitors

Lamontanara A. J., Gencer E. B., Kuzyk O., Hantschel O.

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, vol.1834, no.7, pp.1449-1459, 2013 (SCI-Expanded) identifier identifier identifier


In this article, we are reviewing the molecular mechanisms that lead to kinase inhibitor resistance. As the oncogenic BCR-ABL kinase is the target of the first approved small-molecule kinase inhibitor imatinib, we will first focus on the structural and mechanistic basis for imatinib resistance. We will then show ways how next generations of BCR-ABL inhibitors and alternative targeting strategies have helped to offer effective treatment options for imatinib-resistant patients. Based on these insights, we discuss commonalities and further mechanisms that lead to resistance to other kinase inhibitors in solid tumors. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012). (C) 2012 Elsevier B.V. All rights reserved.