Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors |
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Authors: | Davis S T Benson B G Bramson H N Chapman D E Dickerson S H Dold K M Eberwein D J Edelstein M Frye S V Gampe Jr R T Griffin R J Harris P A Hassell A M Holmes W D Hunter R N Knick V B Lackey K Lovejoy B Luzzio M J Murray D Parker P Rocque W J Shewchuk L Veal J M Walker D H Kuyper L F |
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Institution: | Department of Cancer Biology, Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709, USA. std41085@glaxowellcome.com |
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Abstract: | Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of 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 reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients. |
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