Ciência e terapia do câncer

Cyclic Dependent Kinase (CDK): Role in Cancer Pathogenesis and as Drug Target in Cancer Therapeutics

Abstract

Bekesho Geleta, Eyasu Makonnen and Solomon M Abay

The cell cycle is the process by which mammalian cells regulate proliferation and has S, M, G2 and G1 phase. Loss of these cell-cycle control and increased resistance to apoptosis (programmed cell death) represent major hallmarks of cancer. Cyclic dependent kinases (CDKs), a family of serine/threonine, can control the cell cycle progression and transcription. Besides, they are also involved in regulating mRNA processing, the differentiation of nerve cells and glucose homeostasis. Therefore, CDKs are multiple function proteins. Cellular proliferation, driven by CDKs and their cyclin partners, is decontrolled in cancer; therefore, cancer is considered as a proliferative disorder and targeting the cell cycle, therefore, seems to be a good strategy for new targeted anticancer agents. CDKs activity is closely associated with specific cyclin co-factors and at least 12 separate genetic loci are known to code for the CDKs. Therefore, cyclins are considered to be the gears that are changed to aid the transition between cycle phases. CDKs are generally classified into two major groups, based on whether they control cell cycle progression which includes CDK1 to CDK6 or regulate gene transcription by RNAPII that includes CDK 7, CDK8, CDK9 and CDK19. Increases in level of CDKs are observed in cancer. Inhibition of CDKs, which are the key regulators of the cell-cycle progression and RNA transcription, represents a good strategy for cancer drug discovery and development as well as therapy. This review was briefly described the above-mentioned possible roles of CDKs in the physiological and pathological mechanisms of cancer, further discussing recent advances and challenges in CDKs as a therapeutic target.