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

Learning Objectives After completing this course, the reader will be able to: Describe the basics of cell-cycle regulation.Understand how Rb pathway derangement causes cancer.Relate the clinical findings with flavopiridol and UCN-01 to their mechanisms of action. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com 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.