Possible Interaction: Methionine and Crizotinib

“ Crizotinib is a small-molecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and another proto-oncogene receptor tyrosine kinase, MET.”

“ Crizotinib also inhibited RhoA activation in addition to MET phosphorylation.”

“As a proof of concept, inhibition of Met using crizotinib caused Met-amplified murine tumors to initially undergo complete regression.”

“Both crizotinib and BKM120 strongly inhibited the activity of MET and PI3K as evidenced by the decreased phosphorylation of MET, AKT and ribosomal S6 kinase.”

“ Crizotinib has been shown to be an inhibitor of MET , anaplastic lymphoma kinase (ALK) and ROS1 receptor tyrosine kinases, and is FDA approved for ALK inhibition.”

“Accordingly, H1993 tumors bearing MET amplification showed a mean reduction in [18F]FLT uptake of 28% and 41% after low- and high-dose treatment with crizotinib for 3 days, whereas no posttherapy changes of [18F]FLT uptake were observed in HCC827 tumors lacking MET amplification.”

“Results: Crizotinib and TAS-115 inhibited Met phosphorylation and reversed erlotinib resistance and VEGF production triggered by HGF in PC-9 and HCC827 cells in vitro.”

“Treatment of LU0858 with crizotinib , a small molecule inhibitor for ALK and c‐MET , inhibited tumor growth and c‐MET activity.”

“Although crizotinib , a dual tyrosine kinase inhibitor (TKI) of ALK and Met , shows dramatic effect against EML4-ALK lung cancer cells, these cells can acquire resistance to crizotinib by several mechanisms, including ALK amplification and gatekeeper mutation.”

“Hepatocyte growth factor (HGF) activated Met/Gab1 and triggered resistance to TAE684, but not crizotinib , which inhibits Met.”

“Conclusions: Crizotinib shows a marked antitumor action in MET amplification-positive lung cancer cells but not in cells without MET amplification, including those with a MET mutation.”