The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer

Cell Prolif. 2003 Jun;36(3):131-49. doi: 10.1046/j.1365-2184.2003.00266.x.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Cycle / drug effects*
  • Cell Division
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Cyclins / metabolism
  • Cyclins / physiology*
  • Drug Design
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Biological
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / metabolism
  • Phosphorylation

Substances

  • Antineoplastic Agents
  • Cyclins
  • Enzyme Inhibitors
  • Cyclin-Dependent Kinases