Oncogenic Kinase Bcr-Abl and Its Resistance to Pharmacological Inhibitors

Abstract

The advances in understanding of neoplastic transformation considerably help the design of molecular-targeted therapies. Protein kinases are critical components of cellular signalling pathways and, due to their frequent deregulation in cancer cells, they have become one of the most important targets in drug development. The efficiency of imatinib in the treatment of chronic myeloid leukemia is a strong evidence that kinase inhibitors can be effective drugs, although some patients develop resistance to them. The structure-based design, however, allows synthesis of second-generation drugs, which are able to overcome this resistance. The review focuses on oncogenic Bcr-Abl as an example of a rational target for kinase inhibitors, their development and biochemical properties.