Cancer genomics-based screening of new therapeutic targets and biomarkers for esophageal cancer.

e16514 Background: Since the number of esophageal cancer patients who show objective response to standard therapies is still small, development of new anti-cancer agents with minimum risk of adverse events and highly precise molecular biomarkers is eagerly awaited. Methods: We have been screening novel therapeutic targets and their companion diagnostics for esophageal cancers as follows; i) To identify up-regulated genes in esophageal cancers by the gene expression profile analysis, ii) To verify the candidate genes for their low expression in normal tissues, iii) To validate the clinicopathological significance of their protein expression by tissue microarray covering 265 esophageal cancers, and iv) To verify their function for the growth of the esophageal cancer cells by siRNAs and gene transfection assays. Results: We identified dozens of candidate oncoproteins and selected a metyltransferase ESOC1 (esophageal cancer-associated oncoprotein 1). Immunohistochemical analysis revealed that ESOC1 positivity was observed in 68.5% of esophageal cancers and associated with tumor size. Moreover ESOC1 expression was an independent prognostic factor for esophageal cancer patients. Suppression of ESOC1 expression by its siRNAs inhibited growth of esophageal cancer cell lines. Introduction of ESOC1 increased the growth activity of mammalian cells, suggesting that ESOC1 is likely to be a prognostic biomarker and therapeutic target for esophageal cancers. Conclusions: Cancer genomics-based approach could be useful for the development of new cancer biomarkers as well as therapeutic targets for small molecules, antibodies, nucleic acid drugs, and immunotherapies.