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Targetting Cdks in Cancer: An Overview and New Insights

Abstract

Gousia Chashoo and Ajit Kumar Saxena

The master regulators, cyclin dependant kinases (CDKs), are the actual driving forces behind the progression of cell cycle in eukaryotic cells. The activity level of these kinases is maintained and controlled by the periodic synthesis and degradation of positive regulators, cyclins, negative regulators, cyclin kinase inhibitors (CKIs) and other reversible phosphorylation events. CDK/cyclin complexes regulate each phase of the cell cycle and the breakdown of this regulation in any phase results in uncontrolled growth and thus tumor formation. If not all, most of the cancers show direct or indirect deregulation of these kinases, therefore targeting CDKs is an important mode to develop new anticancer therapeutics. Promising preclinical data of many compounds led to the entry of a few of these compounds into clinical trials where excellent results have maintained the high hopes and the recent discovery of one of these compounds as a commercially available drug has further enriched this area of research. So far much has been said about these essential targets but there is a need to discuss their role, mechanism, avenues and progress timely for further understanding of CDKs as anticancer drug targets and to learn how best new CDK inhibitors could be put into clinically developed agents.

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