Abstract 4763: Targeted therapy by MET inhibitors against small-cell lung cancer with aberrant activation of HGF/MET pathway

Abstract

Small-cell lung cancer (SCLC) is one of the most aggressive malignancy, characterized by rapid growth and metastatic spread to multiple organs. Approximately 70% of SCLC patients have distant metastases at the diagnosis. Recent studies reported some genomic aberrations in SCLC and several molecular target drugs have been evaluated in clinical trials. However, no molecular target agents have been approved yet for SCLC.

Hepatocyte growth factor (HGF), also known as scatter factor, is only one ligand for MET receptor. HGF/MET pathway plays the crucial role in the growth of various types of cancers. The purpose of this study is to examine the role of HGF/MET pathway activation in SCLC and to evaluate therapeutic potential of MET inhibitors, including crizotinib and golvatinib, against metastasized SCLC.

We used eight human SCLC cell lines. Expression of HGF and MET was evaluated by ELISA and western blot, respectively. Cell viability was examined by MTT assay. Four cell lines produced discernible levels of HGF and four cell lines expressed phosphorylated MET, respectively. MET inhibitors, crizotinib and golvatinib, remarkably inhibited the viability of three cell lines, SBC-5, DMS273 and DMS273B1. Knockdown of either MET or HGF by specific siRNA suppressed the growth of these cell lines, indicating that HGF/MET pathway activation is essential for survival of these SCLC cell lines. These observations suggest that MET-TKIs may be useful for a subset of SCLC with aberrant HGF/MET pathway activation.

We recently established in vivo imaging model of multiple organ metastasis (including liver and bone metastases) with SBC-5 cells. We are now evaluating the anti-metastatic effect of MET-TKIs, crizotinib and golvatinib, in the in vivo imaging model. At the annual meeting, we will present the results of MET-TKI treatment and discuss their potential against multiple-organ metastasis produced by SCLC with aberrant HGF/MET pathway activation.

Citation Format: Hirokazu Taniguchi, Shinji Takeuchi, Koji Fukuda, Tadaaki Yamada, Shuichi Sakamoto, Manabu Kawada, Seiji Yano. Targeted therapy by MET inhibitors against small-cell lung cancer with aberrant activation of HGF/MET pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4763.