ABSTRACT
Disruption of cell cycle-regulatory genes frequently occurs in human cancers, including leukemia and lymphoma, and provides a growth advantage to neoplastic cells. As an anticancer strategy, targeting cell cycle as well as transcription-regulatory cyclin-dependent kinases (CDKs) represents a highly attractive approach, particularly in the case of leukemia and lymphoma, in which dysregulation of cell cycle-related genes appears to play an important role in disease pathogenesis and prognosis. Among various CDK inhibitors under development, several are currently undergoing clinical evaluation on the basis of preclinical evidence of antitumor activity. Combination strategies involving the CDK inhibitor UCN-01 have primarily focused on the inhibitors of the Ras/Raf/MEKl/2/ERKl/2 pathway. CDKs and related molecules represent promising targets in the development of cancer therapeutics. In preclinical studies, flavopiridol potently inhibited cell proliferation in all 60 National Cancer Institute human tumor cell lines, with no obvious tumor-type selectivity.
