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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.
Charlotte Julie Caroline Gehin
Didier Trono, Laurence Gouzi Abrami, Evaristo Jose Planet Letschert, Julien Léonard Duc, Laia Simo Riudalbas, Sandra Eloise Kjeldsen, Alexandre Coudray, Sagane Dind