Cyclin-dependent kinase modulators: a novel class of cell cycle regulators for cancer therapy.

With the understanding of the role of cdks in cell cycle regulation and the discovery that approx. 90% of all neoplasias are the result of 'cdk hyperactivation' leading to the abrogation of the Rb pathway, novel ATP competitive cdk inhibitors are being developed. The first two tested in clinical trials, flavopiridol and UCN-01, showed promising results with evidence of antitumor activity and plasma concentrations sufficient to inhibit cdk-related functions. Best schedule to be administered, combination with standard chemotherapeutic agents and demonstration of cdk modulation from tumor samples from patients in these trials are important issues that need to be answered in order to obtain the best possible results with these agents.