Identification of kinases and kinase inhibitors for the differential targeting of Wnt/β-catenin signaling in gastric cancer subtypes.

The oncogenic signaling pathway Wnt is often activated in many cancers including gastric cancer. Wnt signaling pathway is considered as a potential target for developing new targeted therapeutics. Kinase inhibitors are the promising class of drugs for many diseases including cancers. Toward identifying the potent inhibitors targeting Wnt signaling pathway, a kinase inhibitor library with 82 inhibitors were screened using Wnt pathway reporter assay in gastric cancer cells. Notably, 34 kinase inhibitors were identified to inhibit Wnt mediated reporter activity to the extent of more than 50%. The corresponding kinase genes, which are known targets of these kinase inhibitors, were investigated for their expression in the available mRNA profiles of gastric tumors. A major group of the kinase genes showed higher expression in intestinal subtype gastric tumors. Another group of kinase genes were found expressed in diffuse type gastric tumors. The kinase genes expressed in intestinal type gastric tumors were found associated with varying survival of gastric cancer patients whereas those expressed in diffuse type tumors were found associated with the poor survival. Thus, the kinase genes specifically expressed in intestinal and diffuse type gastric tumors and the kinase inhibitors to target Wnt signaling pathway in gastric cancer subtypes have been identified.