The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer.
The cell cycle is controlled by numerous mechanisms ensuring correct cell division. This review will focus on these mechanisms, i.e. regulation of cyclin-dependent kinases (CDK) by cyclins, CDK inhibitors and phosphorylating events. The quality checkpoints activated after DNA damage are also discussed. The complexity of the regulation of the cell cycle is also reflected in the different alterations leading to aberrant cell proliferation and development of cancer. Consequently, targeting the cell cycle in general and CDK in particular presents unique opportunities for drug discovery. This review provides an overview of deregulation of the cell cycle in cancer. Different families of known CDK inhibitors acting by ATP competition are also discussed. Currently, at least three compounds with CDK inhibitory activity (flavopiridol, UCN-01, roscovitine) have entered clinical trials.
Vermeulen
Katrien
K
Faculty of Medicine, Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium.
Van Bockstaele
Dirk R
DR
Berneman
Zwi N
ZN
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism / Q000502:physiology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D010766:Phosphorylation
D000970:Antineoplastic Agents; D016213:Cyclins; D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases