Abstract

CANCER CHEMOTHERAPY AND CYCLIN DEPENDENT KINASES

Mageshwaran Lakshmanan*, Veerendra V, Patric Joshua P

Abstract

Protein kinases play a central role in the regulation of various cell processes including proliferation, cell cycle, differentiation and apoptosis through phosphorylation. Dysregulation of these critical cellular processes, due to the abnormal expression of some of these proteins, is common in many cancers. CDK inhibition can initiate apoptosis and could be particularly useful in treating of various malignancies. In many human cancers CDK/Cyclins are dysregulated, which affect the coordinated cycle of cell growth and proliferation leading contribution to the uncontrolled proliferation characteristic of cancer cells. Therefore the pharmacological inhibition of CDKs can cause cell cycle arrest and induces apoptosis selectively in transformed cells. To date, significant progress has been made in the development of specific CDKs inhibitors. However, the main drawback is to know which CDK or CDK/cyclin should be targeted for selective action so that other vital cellular function can be avoided. After Palbociclib, drugs like dinaciclib, PHA-848125 AC, BAY-1000394 are leading the way. This article reviews about the role and clinical implications of CDKs in cancer chemotherapy, rationale for targeting CDKs and strategies in development of CDK inhibitors.

Keywords: Cyclin dependent kinase, imatinib, cancer chemotherapy.