Emerging Role of Aurora Kinase Inhibitors in Chronic Myeloid Leukemia

Abstract

Abstract Resistance to imatinib and second-generation tyrosine kinase inhibitors is an ongoing problem most frequently mediated through mutations of the Bcr-Abl kinase domain. One mutation that affects responsiveness to all current available agents is T315I. Aurora proteins belong to a small family of serine/threonine kinases that are essential for proliferating cells and have been identified as key regulators of different steps in mitosis and meiosis, ranging from the formation of the mitotic spindle up to cytokinesis. Unexpectedly, Aurora kinase inhibitors have been found to have activity against the T315I bcr-abl mutation, and some of them might rise as important therapeutic options. The common mechanism of action for protein kinase inhibition is competition with adenosine triphosphate for the active site-binding pocket, which is very similar among the protein kinases, and this could explain the cross-reactivity. Herein, we discuss the basics of imatinib resistance development and Aurora kinase biology, and describe a selected group of Aurora kinase inhibitors with potential activity in this patient population.