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Biochim Biophys Acta. 2013 Jul;1834(7):1449-59. doi: 10.1016/j.bbapap.2012.12.009. Epub 2012 Dec 28.

Mechanisms of resistance to BCR-ABL and other kinase inhibitors.

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École polytechnique fédérale de Lausanne EPFL, School of Life Sciences, Swiss Institute for Experimental Cancer Research ISREC, Lausanne, Switzerland.


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).

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