MET-RON dual inhibitor, BMS-777607, suppresses cholangiocarcinoma cell growth, and MET-RON upregulation indicates worse prognosis for intra-hepatic cholangiocarcinoma patients

Abstract

Intra-hepatic cholangiocarcinoma (CCA) is an aggressive cancer with few effective therapeutic options. MET and RON have been found to be increased in a variety of tumors and to be associated with tumor progression and acquired resistance to therapy. The present study evaluated the efficacy of a MET-RON dual inhibitor (BMS-777607) for treating CCA and analyzed the prognostic significance of MET-RON upregulation. We treated CCA cell lines and rats with CCA with BMS-777607 to determine its effects on tumor growth and measured the MET-RON protein expression in samples obtained from 96 patients with CCA who previously underwent hepatectomies. A clonogenic assay revealed that BMS-777607 inhibited the growth of HuCCT1 and KKU-100 human CCA cells. It also decreased tumor growth in CCA rats. MET-RON upregulation independently predicted poor survival for CCA patients who previously underwent hepatectomies. In conclusion, MET-RON upregulation is a poor prognostic factor in CCA patients receiving hepatectomies and may be targeted using BMS-77760.