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The Cell Cycle as a Target for Cancer Therapy: Basic and Clinical Findings with the Small Molecule Inhibitors Flavopiridol and UCN-01

Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA

Correspondence: Adrian M. Senderowicz, M.D., National Institutes of Health, Oral and Pharyngeal Cancer Branch, NIDCR Building 30; Room 211, 30 Convent Drive, Bethesda, Maryland 20892-4340, USA. Telephone: 301-594-5270; Fax: 301-402-0823; e-mail: asenderowicz{at}dir.nidcr.nih.gov

Many tumor types are associated with genetic changes in the retinoblastoma pathway, leading to hyperactivation of cyclin-dependent kinases and incorrect progression through the cell cycle. Small-molecule cyclin-dependent kinase inhibitors are being developed as therapeutic agents. Of these, flavopiridol and UCN-01 are being explored in cancer patients in phase I and phase II clinical trials, both as single agents and in combination with conventional chemotherapeutic agents. The present article discusses the mechanisms of action of flavopiridol and UCN-01 as well as the outcome of clinical trials with these novel agents.

Key Words. Cell cycle • Cyclin-dependent kinases • Flavopiridol • UCN-01 • Phase I trials • Clinical trials

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