Cell Cycle, CDKs and Cancer: A Changing Paradigm

Nat Rev Cancer. 2009 Mar;9(3):153-66. doi: 10.1038/nrc2602.

Abstract

Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity. Misregulated CDKs induce unscheduled proliferation as well as genomic and chromosomal instability. According to current models, mammalian CDKs are essential for driving each cell cycle phase, so therapeutic strategies that block CDK activity are unlikely to selectively target tumour cells. However, recent genetic evidence has revealed that, whereas CDK1 is required for the cell cycle, interphase CDKs are only essential for proliferation of specialized cells. Emerging evidence suggests that tumour cells may also require specific interphase CDKs for proliferation. Thus, selective CDK inhibition may provide therapeutic benefit against certain human neoplasias.

Trial registration: ClinicalTrials.gov NCT00141297 NCT00147485 NCT00292864 NCT00372073 NCT00390117 NCT00400296 NCT00407498 NCT00446342 NCT00772876.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle*
  • Cell Proliferation
  • Chromosomal Instability
  • Chromosome Aberrations
  • Cyclin D
  • Cyclin E / physiology
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / physiology*
  • Cyclins / physiology
  • DNA Damage
  • Humans
  • Mitosis
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Neoplastic Stem Cells / cytology
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Cyclin D
  • Cyclin E
  • Cyclins
  • Protein Kinase Inhibitors
  • Cyclin-Dependent Kinases

Associated data

  • ClinicalTrials.gov/NCT00141297
  • ClinicalTrials.gov/NCT00147485
  • ClinicalTrials.gov/NCT00292864
  • ClinicalTrials.gov/NCT00372073
  • ClinicalTrials.gov/NCT00390117
  • ClinicalTrials.gov/NCT00400296
  • ClinicalTrials.gov/NCT00407498
  • ClinicalTrials.gov/NCT00446342
  • ClinicalTrials.gov/NCT00772876