The curative effect for patients with advanced gastric cancer is still unsatisfactory. Proton pump inhibitors could be a promising treatment strategy that could sensitize gastric cancer cells to antitumor drugs further; however, the underlying molecular mechanism remains to be further elucidated. In this research, it was found that omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. Interestingly, omeprazole pretreatment enhanced the total m6A level of cells due to the decreased FTO. TCGA analysis showed that FTO expression is up-regulated in GC tissues and is negatively correlated with disease-free survival of GC patients. It was also found that FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. The present study, for the first time, found that m6A modification and its eraser FTO may play a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

8069 Background: To compare therapeutic effects of immediate vs. delayed gefitinib used for advanced non-small cell lung cancer (NSCLC) patients who obtained disease control (DC) after front-line chemotherapy in Chinese population. Methods: The study included 121 Chinese with advanced NSCLC treated with standard chemotherapy and obtained DC followed by either immediate gefitinib (66 cases) or delayed gefitinib, i.e. when tumors progressed (55 cases). The disease control rate (DCR), median progression-free survival time (PFS), median overall survival time (OS) of the two groups were analyzed. The impact of EGFR mutation status on the treatments was also evaluated. Results: The median PFS of patients treated in the immediate treatment setting was significantly longer than that of patients without gefitinib treatment (15.23 months versus 8.13 months,P<0.001). However, the overall median PFS was similar in patients treated with either immediate or delayed settings (15.23 months and 16.23 months respectively, P=0.450). There was no significant difference in OS between the two groups. Although patients whose tumors had EGFR mutation showed a longer median PFS compared to those without the mutation in both treatment groups, similar overall PFS was observed between the groups for patients with EGFR mutation (18.75 months and 18.30 months for maintenance and second-line groups, respectively). Conclusions: Immediate gefitinib use may improve PFS for Chinese patients with advanced NSCLC after front-line chemotherapy. However, similar PFS may be achieved by delayed use of gefitinib. No significant financial relationships to disclose.