BCR ABL Kinase Inhibitors for Cancer Therapy

Abstract

BCR-ABL tyrosine kinase inhibitors have started era of molecular targeted therapy and marked a greatest milestone in cancer drug discovery. Despite of impressive cytogenetic response rates achieved with several agents in patients with chronic myelogenous leukemia (CML) in chronic phase, those with advanced stage CML frequently obtain more modest responses that are in many instances of short duration. Several mechanisms of resistance to imatinib are also observed among patients that develop clinical resistance to imatinib. Some approaches are being pursued to overcome these mutations. Deregulated tyrosine kinase activity of the BCR-ABL fusion protein has been established as the causative molecular event in CML. BCR-ABL tyrosine kinase is an ideal target for pharmacological inhibition. Following the initial success of imatinib as frontline therapy for CML, several second generation therapeutic inhibitors have been developed with increased potency and the ability to inhibit the majority of imatinib resistant mutations. In addition, many other protein kinases implicated in signaling transduction downstream BCR-ABL play critical roles in the pathogenesis of CML, thus representing potential therapeutic targets revealed from several clinical studies. The objective of present article is on current developments of potential existing and new innovative BCR-ABL kinase inhibitors for tumor therapy and specificity of several new inhibitors.