Cyclins and related kinases in cancer cells

J BUON. 2007 Sep;12 Suppl 1:S45-52.

Abstract

Tumor cell proliferation is frequently associated with genetic or epigenetic alterations in key cell cycle molecules that regulate the activity of cyclin-dependent kinases (CDKs). These protein kinases control the progression through the different phases of the cell division cycle. Tumor-associated alterations in their activating partners, cyclins, or in CDK inhibitors help to sustain proliferation with independence from external mitogenic or anti-mitogenic signals. The significant frequency of these alterations in human cancer and recent studies in genetically-engineered mouse models predict that inhibition of CDKs might have therapeutic value. Most interphase CDKs are dispensable for mouse development but their inhibition may prevent DNA replication in some specific tumor cells. On the other hand, inactivation of mitotic CDKs efficiently prevents progression throughout the mitotic cell cycle. The combination of biochemical and genetic data on the function of these regulators will be instrumental to define new targeted therapies for inhibiting proliferation in cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Cycle* / drug effects
  • Cell Cycle* / genetics
  • Cell Proliferation* / drug effects
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Cyclins / genetics
  • Cyclins / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Antineoplastic Agents
  • Cyclins
  • Protein Kinase Inhibitors
  • Cyclin-Dependent Kinases