Tivantinib does not inhibit MET function.

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Tivantinib does not inhibit MET function. Tivantinib does not inhibit MET function. A, Sensitivity of 35 liver cancer cell lines to tivantinib. The heatmaps below represent for each cell line (columns) tivantinib sensitivity using the AUC and MET status at the mRNA (qRT-PCR), protein (RPPA), and genomic (copy number analyzed by exome sequencing) levels. AUC of 1, no drug response. Copy number, mRNA, and protein levels for each cell line are expressed relative to the mean value of normal noncirrhotic liver tissues. Associations between tivantinib AUC and MET status were analyzed using Spearman test. Represented below the heatmap are chromosomal aberrations identified in the MHCC97H cell line showing focal amplification of MET gene. B, Scatter plots showing correlations between sensitivity patterns assessed by the AUC of two selective MET inhibitors (PHA-665752 and JNJ-38877605) and tivantinib among 35 liver cancer cell lines. Correlation for each drug pair was assessed using Spearman test. C, Western blot analysis of MET phosphorylation and its downstream effectors AKT and ERK1/2 in two MET-dependent cell lines (MHCC97H and HCC-3) treated 4 hours with increasing doses of PHA-665752, JNJ-38877605, or tivantinib. Sandra Rebouissou et al. Clin Cancer Res 2017;23:4364-4375 ©2017 by American Association for Cancer Research