Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors

Most traditional cytotoxic anticancer agents ablate the rapidly dividing ep ithelium of the hair follicle and induce alopecia (hair Loss). Inhibition o f cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducin g the sensitivity of the epithelium to many cell cycle-active antitumor age nts. Potent small-molecule inhibitors of CDK2 were developed using structur e-based methods. Topical application of these compounds in a neonatal rat m odel of CIA reduced hair loss at the site of application in 33 to 50% of th e animals. Thus, inhibition of CDK2 represents a potentially useful approac h for the prevention of CIA in cancer patients.