Cyclin-dependent kinase modulators and cancer therapy

Abstract

The cell cycle of eukaryotic cells varies greatly from species to species and tissue to tissue. Since an erroneous control of the cell cycle can have disastrous consequences for cellular life, there are genetically programmed signals, so-called cell cycle checkpoints, which ensure that all events of each stage are completed before beginning the next phase. Among the numerous molecules involved in this process, the most important are the cyclin-dependent kinases (CDKs), proteins that are activated only when bound to cyclins (regulatory proteins with fluctuating concentrations). In general, more CDKs are overexpressed in cancer cells than in normal cells, which explains why cancer cells divide uncontrollably. Succeeding in modulating CDK activity with pharmacological agents could result in decreasing the abnormal proliferation rate of cancer cells. This review offers an overview of CDK-cyclin complexes in relation to different cell cycle phases, an analysis of CDK activation and inhibition of molecular mechanisms, and an extensive report, including clinical trials, regarding four new drugs acting as CDK modulators: alvocidib, P276-00, SNS-032 and seliciclib.