Report

Prevention of Chemotherapy-Induced Alopecia in Rats by CDK Inhibitors

Science  05 Jan 2001:
Vol. 291, Issue 5501, pp. 134-137
DOI: 10.1126/science.291.5501.134

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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.

  • * To whom correspondence should be addressed. E-mail: std41085{at}glaxowellcome.com

  • Present address: Neurocrine Biosciences, 10555 Science Center Drive, San Diego, CA 92121, USA.

  • Present address: Pennie & Edmonds LLP, 3300 Hillview Avenue, Palo Alto, CA 94304, USA.

  • § Present address: Pfizer Inc., Pfizer Central Research, Eastern Point Road, Groton, CT 06340, USA.

  • || Present address: Hoffman–La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA.

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