Cell Cycle Kinases as Therapeutic Targets for Cancer

Nat Rev Drug Discov. 2009 Jul;8(7):547-66. doi: 10.1038/nrd2907.

Abstract

Several families of protein kinases orchestrate the complex events that drive the cell cycle, and their activity is frequently deregulated in hyperproliferative cancer cells. Although several molecules that inhibit cell cycle kinases have been developed and clinically screened as potential anticancer agents, none of these has been approved for commercial use and an effective strategy to specifically control malignant cell proliferation has yet to be established. However, recent genetic and biochemical studies have provided information about the requirement for certain cell cycle kinases by specific tumours and specialized tissue types. Here, we discuss the potential and limitations of established cell cycle kinases as targets in anticancer drug discovery as well as novel strategies for the design of new agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aurora Kinases
  • Cell Cycle
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / chemistry
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • DNA Damage
  • Humans
  • Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / chemistry
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / chemistry
  • Retinoblastoma-Like Protein p130 / physiology
  • Staurosporine / analogs & derivatives
  • Staurosporine / therapeutic use

Substances

  • Cell Cycle Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Retinoblastoma-Like Protein p130
  • 7-hydroxystaurosporine
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Cyclin-Dependent Kinases
  • Staurosporine