Development of Tivantinib as Treatment for Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is a rapidly rising cause of liver-related death worldwide. Most patients are diagnosed at an advanced stage of disease, when systemic therapy is the only viable option for treatment. Significant strides have been made in the molecular understanding of HCC development and growth stimulation. The c-Met pathway has been found to be an important pathway in half of all patients with HCC. HCC tumors with high c-Met activation are associated with an aggressive phenotype and poor prognosis. Tivantinib is a MET receptor tyrosine kinase inhibitor with a broad spectrum of anti-tumor effects currently being studied for the treatment of HCC. Phase I and II data are available for tivantinib in the treatment of solid tumors, including HCC. There appears to be an adequate safety profile, with the main side-effect being neutropenia. In HCC patients with elevated c-Met activity, tivantinib results in an improved time to progression of 2.7 months, compared with 1.4 months in placebo-treated patients. Further studies are ongoing, but early data suggest that tivantinib is a therapy that deserves close attention in the coming years for patients with HCC.
Division of Gastroenterology, Department of Medicine, Scripps Green Hospital, La Jolla, CA.
Jennifer
J
Au
Scripps Center for Organ and Cell Transplantation, Scripps Green Hospital, La Jolla, CA.
Catherine
C
Frenette
Hepatocellular carcinoma; Liver cancer; Tivantinib; Tyrosine kinase inhibitor; c-Met