Effect of metformin on hypoxia-associated gene expression in oral cavity squamous cell carcinoma in non-diabetic patients - a prospective window of opportunity study.

Purpose Research suggests that metformin may reduce tumor hypoxia, rendering it a potential radiosensitizer. This study investigated metformin's effect on hypoxia-associated gene expression in oral cavity squamous cell carcinoma (OCSCC).Methods In this prospective trial, non-diabetic patients with OCSCC scheduled for curative surgery received preoperative metformin for 10 to 14 days. Tumor biopsies were taken before and after metformin treatment. Gene expression profiling was performed using RNASeq, emphasizing on hypoxia-associated signaling pathways.Results Fifteen patients of 25 enrolled patients completed the study protocol and passed quality checks. No significant difference in gene expression was observed after adjustment for multiple testing. No significant changes were found in the hypoxia-associated hypoxia-inducible factor 1- alpha (HIF1A) pathway or in other signaling pathways associated with metformin reported in the literature.Conclusion This study does not support the hypothesis that metformin improves tumor hypoxia in OCSCC after 10 to 14 days of treatment.