Cell cycle--molecular mechanisms and therapeutic perspectives in oncology

Regulation of cell division is an object of intensive studies for the needs of tumor biology and medicine. Cyclins and cyclin-dependent kinases are the major regulatory complexes that control the transition from one phase of the cell cycle to the following one. It has been established that the activity of certain cyclins is impaired in some tumors due to mutation of the coding gene. Verification of the specific change in a particular cyclin is discussed as a reliable diagnostic marker in clinical oncology. Mutations in genes for inhibitors of cyclin-dependent kinases correspond with definite tumor types. Impairment of control mechanisms leads to independence of cell division from signal regulators, which lies at the basis of tumorigenesis. Malignant transformation could result from overexpression of positive regulators like cyclins or loss of negative regulators like the inhibitors of the cyclin-dependent kinases. These molecules are an object of the new chemo- and gene therapeutical antitumor strategies. The present review focuses on the main regulatory points in cell cycle phases and on the pharmacological agents that affect them. Novel antitumor strategies based on the influence on the molecular mechanisms regulating the cell cycle are discussed.