Factors underlying sensitivity of cancers to small-molecule kinase inhibitors

Nat Rev Drug Discov. 2009 Sep;8(9):709-23. doi: 10.1038/nrd2871. Epub 2009 Jul 24.


Selective small-molecule kinase inhibitors have emerged over the past decade as an important class of anti-cancer agents, and have demonstrated impressive clinical efficacy in several different diseases, including relatively common malignancies such as breast and lung cancer. However, clinical benefit is typically limited to a fraction of treated patients. Genomic features of individual tumours contribute significantly to such clinical responses, and these seem to vary tremendously across patients. Additional factors, including pharmacogenomics, the tumour microenvironment and rapidly acquired drug resistance, also contribute to the clinical sensitivity of various cancers, and should be considered and applied in the development and use of new kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Drug Design
  • Drug Resistance, Neoplasm
  • Humans
  • Neoplasms / drug therapy*
  • Oncogenes / drug effects
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Small Molecule Libraries


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Small Molecule Libraries
  • Protein Kinases