Suppression of MET Signaling Mediated by Pitavastatin and Capmatinib Inhibits Oral and Esophageal Cancer Cell Growth.

Despite increasing knowledge on oral and esophageal squamous cell carcinoma (OSCC and ESCC), specific medicines against both have not yet been developed. Here, we aimed to find novel anticancer drugs through functional cell-based screening of an FDA-approved drug library against OSCC and ESCC. Pitavastatin, an HMGCR inhibitor, emerged as an anticancer drug that inhibits tumor growth by downregulating AKT and ERK signals in OSCC and ESCC cells. One of the mechanisms by which pitavastatin inhibits cell growth might be the suppression of MET signaling through immature MET due to dysfunction of the Golgi apparatus. Moreover, the sensitivity of tumor growth to pitavastatin might be correlated with GGPS1 expression levels. In vivo therapeutic models revealed that the combination of pitavastatin with capmatinib, a MET-specific inhibitor, dramatically reduced tumor growth. Our findings suggest that GGPS1 expression could be a biomarker in cancer therapy with pitavastatin, and the combination of pitavastatin with capmatinib might be a promising therapeutic strategy in OSCC and ESCC. IMPLICATIONS: This study provides new insight into the mechanism of pitavastatin as an anticancer drug and suggests that the combination of pitavastatin with capmatinib is a useful therapeutic strategy in OSCC and ESCC. ©2020 American Association for Cancer Research.