Cellular growth,development,and differentiation are tightly controlled by a conserved biological mechanism:the cell cycle.This cycle is primarily regulated by cyclin-dependent kinase(CDK)-cyclin complexes,checkpoint k...Cellular growth,development,and differentiation are tightly controlled by a conserved biological mechanism:the cell cycle.This cycle 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 in tumorigenesis,several cell cycle inhibitors have emerged as potential therapeutic drugs for the treatment of cancers-both as singleagent therapy and in combination with traditional cytotoxic or molecular targeting agents.In this review,we discuss the mechanisms underlying cell cycle regulation and present small-molecule anticancer drugs that are under development,including both pan-CDK inhibitors and CDK4/6-selective inhibitors.In addition,we provide an outline of some promising CDK inhibitors currently in preclinical and clinical trials that target cell cycle abnormalities in various cancers.展开更多
文摘Cellular growth,development,and differentiation are tightly controlled by a conserved biological mechanism:the cell cycle.This cycle 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 in tumorigenesis,several cell cycle inhibitors have emerged as potential therapeutic drugs for the treatment of cancers-both as singleagent therapy and in combination with traditional cytotoxic or molecular targeting agents.In this review,we discuss the mechanisms underlying cell cycle regulation and present small-molecule anticancer drugs that are under development,including both pan-CDK inhibitors and CDK4/6-selective inhibitors.In addition,we provide an outline of some promising CDK inhibitors currently in preclinical and clinical trials that target cell cycle abnormalities in various cancers.
