Molecular basis for sunitinib efficacy and future clinical development.
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.
Faivre
Sandrine
S
Service Inter-Hospitalier de Cancérologie (SIHC) Beaujon-Bichat and RayLab, Hôpital Beaujon, APHP and Denis Diderot University, 100 Boulevard du Général Leclerc, 92118 Clichy Cedex, France.
Demetri
George
G
Sargent
William
W
Raymond
Eric
E
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib