Tivantinib (ARQ 197) is designed to block the activity of c-MET, a molecule that plays multiple key roles in human cancer including cancer cell growth,survival, angiogenesis, invasion and metastasis in nsNSCLC (non squamous Non-Small Cell Lung Cancer). c-Met is inappropriately expressed in almost all types of human cancer, with an established role in tumor development. Tivantinib’s mode-of-action story is told in 3 steps:

a) Both EGFR and c-METsignaling can drive nonsquamous non-small cell lung cancer (nsNSCLC).
b) Inhibiting EGFRsignaling is a standard approach to blocking nsNSCLC. However, c-MET can compensate for the loss of EGFR signaling, allowing tumors to progress.
c) Tivantinib selectively blocks c-METsignaling. When combined with the EGFR inhibitor erlotinib, 2 critical oncogenic signaling axes can be stopped, halting the progression of nsNSCLC.