Targeting nuclear kinases in cancer: development of cell cycle kinase inhibitors

Pharmacol Ther. 2014 May;142(2):258-69. doi: 10.1016/j.pharmthera.2013.12.010. Epub 2013 Dec 19.

Abstract

Cellular proliferation is a tightly controlled set of events that is regulated by numerous nuclear protein kinases. The proteins involved include checkpoint kinases (CHK), cyclin-dependent kinases (CDK), which regulate the cell cycle and aurora kinases (AURK) and polo-like kinases (PLK), which regulate mitosis. In cancer, these nuclear kinases are often dysregulated and cause uncontrolled cell proliferation and growth. Much work has gone into developing novel therapeutics that target each of these protein kinases in cancer but none have been approved in patients. In this review we provide an overview of the current compounds being developed clinically to target these nuclear kinases involved in regulating the cell cycle and mitosis.

Keywords: Cell cycle inhibitors; DNA damage response; Mitosis inhibitors; Nuclear kinase inhibitor.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimitotic Agents / therapeutic use*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / metabolism
  • Drug Design
  • Humans
  • Mitosis / drug effects
  • Molecular Targeted Therapy*
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects

Substances

  • Antimitotic Agents
  • Protein Kinase Inhibitors
  • Cyclin-Dependent Kinases