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Background Aberrant expression of mucins can promote the epithelial-mesenchymal transition (EMT), which leads to enhanced tumorigenesis. Carcinogenesis-related pathways involving c-MET and β-catenin involve mucins. Among the mucins, MUC5AC and MUC6 are characteristic for stomach mucins. This study characterized expressions of MET, MUC5AC, MUC5B, and MUC6 EMT signaling in human gastric cancer (GC) cell lines, and further characterized the differential susceptibility of these cell lines to tepotinib. Methods We assessed the antitumor activity of tepotinib in GC cell lines. The effect of tepotinib on cell viability (IC50), apoptotic cell death, the EMT, and c-MET and β-catenin signaling were evaluated by MTS, flow cytometry, western blotting, and qRT-PCR. Antitumor efficacy was assessed in MKN45 xenograft mice. Results Tepotinib treatment showed dose-dependent growth inhibition of c-MET-amplified SNU620, MKN45, and KATO III cells with concomitant induction of apoptosis, but tepotinib treatment did not have an effect on c-MET-reduced MKN28 and AGS cells. Tepotinib treatment also significantly reduced expressions of phosphor-c-MET, total c-MET, phosphor-ERK, total ERK, beta-catenin, and c-MYC protein in SNU620 and MKN45 cells. In contrast, this drug was only slightly active against KATO III cells. Notably, tepotinib significantly reduced the expressions of EMT promotion genes such as MMP7, COX-2, WNT1, MUC5B, and c-MYC in c-MET-expressed GC cells, and increased expressions of EMT suppression genes such as MUC5AC, MUC6, GSK3β, and ECAD. In a murine xenograft model, tumor volumes were significantly reduced in the tepotinib-treated group, when administered by daily oral gavage at a dose of 10 mg/kg/day. Histologically, tepotinib induced more necrosis than in the control group. Conclusions These results are consistent with clinical evaluations of tepotinib in c-MET and MUC5B-expressed GCs. Editorial acknowledgement National R&D Program for Cancer Control, Ministry of Health and Welfare (HA17C0054), the National Research Foundation of Korea grant funded by the Korean Ministry of Science and ICT (NRF-2017R1A2B4005055), the Ministry of Food and Drug Safety (awarded in 2018, 18183MFDS491) of Korea, the Hallym University Medical Center Research Fund, and the Hallym University Internal Translational Research Fund (No. HURF-2015-38). Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Many patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care. Patients and methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980–2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013. Results The search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis. Conclusion This meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer. [ABSTRACT FROM AUTHOR]