Early development of sunitinib in hepatocellular carcinoma.
Sunitinib malate is an oral, multitargeted receptor tyrosine kinase inhibitor of VEGF receptors 1, 2 and 3; PDGF receptors alpha and beta, and other receptor tyrosine kinases implicated in tumor growth, angiogenesis and metastasis. Hepatocellular carcinoma (HCC) is a highly vascular tumor that overexpresses several angiogenic factors; VEGF and PDGF signaling pathways play a key role in HCC. Until recently, treatment options for advanced HCC were limited and conventional therapies have met with poor response rates. Sorafenib provided proof-of-concept for molecularly targeted therapy in advanced HCC and has recently been approved for treatment. However, not all patients can tolerate sorafenib and patients may experience tumor progression; therefore, additional treatment options are warranted. Sunitinib has shown early evidence of anti-tumor activity in Phase II trials in US, European and Asian patients with locally advanced, unresectable and metastatic HCC. A Phase III trial of sunitinib in HCC is ongoing.
Zhu
Andrew X
AX
Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. azhu@partners.org
Raymond
Eric
E
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy*; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib