Pro-apoptotic and anti-proliferative mechanisms of the kinase inhibitor tivantinib (ARQ 197)

Purpose: Tivantinib is a c-MET inhibitor which demonstrated clinical benefit as a second line treatment of hepatocellular carcinoma (HCC). Since its efficacy was predicted by elevated expression of c-MET in a phase 2 randomized trial, a phase 3 trial in patients selected according to c-MET expression has been initiated. Yet, the mechanisms of action of this new drug and its dependency of its efficacy on c-MET are unclear. Experimental design: To address these issues, analysis of cell viability, apoptosis, cell cycle and of the underlying molecular changes were conducted in HCC and other cancer cells after incuba…