Abstract 50P
Background
In gastric cancer (GC), MET and EGFR amplification have been identified in 2∼24% and 27∼64% of patients, respectively. This study characterized 286 carcinogenesis-related gene alterations and copy number variation (CNV) in four human GC cell lines, and analyzed difference in the susceptibilities of these cells to pelitinib, tepotinib, and docetaxel.
Methods
Using a next-generation sequencing panel, we evaluated the 286 gene alterations and CNV in four GC cells. We also assessed the antitumor activity of pelitinib, tepotinib, and docetaxel in the GC cell lines and a xenograft model. The effects of pelitinib, tepotinib, and docetaxel on cell viability (IC50), apoptotic cell death, tumor volume, and H&E staining were evaluated by MTS (cell proliferation assay) and flow cytometry. Antitumor efficacy was assessed in MKN45 xenograft mice.
Results
Compared to tepotinib, pelitinib inhibited the growth of GC cells with a gained EGFR (CNV > 3, without HRAS, KRAS, and NRAS mutations) and amplified MET (CNV > 30) in a dose-dependent manner with a concomitant induction of cell death. In the murine xenograft model, tumor volumes were significantly reduced in the pelitinib, tepotinib, and docetaxel-treated groups when administered by daily oral gavage at doses of 10, 10, and 5 mg/kg/day respectively. Histologically, pelitinib, tepotinib, and docetaxel induced more necrosis than that observed in the control group.
Conclusions
Pelitinib has anti-tumor activity not only in EGFR gain GCs without mutated HRAS, KRAS and NRAS but also in MET amplified GCs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The research was funded by the Korea Health Technology R&D Project (grant number HI22C1375), the National Research and Development Program for Cancer Control (grant number HA17C0054) of the Ministry of Health and Welfare, and the Hallym University Research Fund.
Disclosure
All authors have declared no conflicts of interest.