Molecular basis for sunitinib efficacy and future clinical development

Nat Rev Drug Discov. 2007 Sep;6(9):734-45. doi: 10.1038/nrd2380.


Sunitinib malate (SU11248/Sutent; Pfizer) is a multitargeted tyrosine kinase inhibitor that has potent anti-angiogenic and antitumour activities. Definitive efficacy has been demonstrated in advanced renal cell carcinoma and in gastrointestinal stromal tumours that are refractory or intolerant to imatinib (Gleevec; Novartis), which has provided the basis for the recent regulatory approvals for these indications. This article summarizes the discovery and development of sunitinib, and discusses key issues for the multitargeted approach in cancer treatment, such as markers of response and development of resistance, and their significance for the future development of sunitinib and other multikinase inhibitors.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors* / adverse effects
  • Angiogenesis Inhibitors* / pharmacology
  • Angiogenesis Inhibitors* / therapeutic use
  • Animals
  • Clinical Trials as Topic
  • Drug Design*
  • Drug Resistance, Neoplasm
  • Humans
  • Indoles* / adverse effects
  • Indoles* / pharmacology
  • Indoles* / therapeutic use
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrroles* / adverse effects
  • Pyrroles* / pharmacology
  • Pyrroles* / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / biosynthesis
  • Sunitinib
  • Vascular Endothelial Growth Factor A / biosynthesis


  • Angiogenesis Inhibitors
  • Indoles
  • Pyrroles
  • Vascular Endothelial Growth Factor A
  • Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • Sunitinib