Cell cycle regulation and anticancer drug discovery

Jingwen Bai, Yaochen Li, Guojun Zhang

Abstract


Cellular growth, development, and differentiation are tightly controlled by a conserved biological mechanism: the cell cycle. Thiscycle is primarily regulated by cyclin-dependent kinase (CDK)-cyclin complexes, checkpoint kinases, and CDK inhibitors.Deregulation of the cell cycle is a hallmark of the transformation of normal cells into tumor cells. Given its importance intumorigenesis, several cell cycle inhibitors have emerged as potential therapeutic drugs for the treatment of cancers-both as singleagenttherapy and in combination with traditional cytotoxic or molecular targeting agents. In this review, we discuss themechanisms underlying cell cycle regulation and present small-molecule anticancer drugs that are under development, includingboth pan-CDK inhibitors and CDK4/6-selective inhibitors. In addition, we provide an outline of some promising CDK inhibitorscurrently in preclinical and clinical trials that target cell cycle abnormalities in various cancers.

Keywords


Cell cycle regulation; cyclin-dependent kinases (CDK); cyclin; pan-CDK inhibitors; CDK4/6-selective inhibitors

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