Targeted therapy to gastric cancer

Abstract

Gastric cancer is a leading cause of death in Asia and a heterogeneous disease. The aim of targeted therapy is to specifically induce cancer cells apoptosis with minimum side effects on normal cells. In this study, 17 gastric cancer cell lines were used to screen a library of 60 small molecule inhibitors and chemotherapy drugs for discovery of potential therapeutic agent by methyl thiazole tetrazolium (MTT) assays. 8 effective drugs which include Docetaxel, Paclitaxel, 17-DMAG, Bortezomib, Calyculin A, Okadaic acid, Staurosporine and Bafilomycin A1 were identified and subject to further characterization by IC50 calculation, cell migration assay, morphology study and cell cycle analysis by FACS. The 8 small molecule compounds were shown to be effective in inhibiting gastric cancer cell growth at nanomolar concentrations in vitro. These drugs’ targets: HSP90, proteasome, protein phosphatase and V-ATPase provide insights for drug design trend for gastric cancer therapy. Unlike drugs that target specific kinases, the 8 drugs identified here indirectly inhibit multiple signaling pathways which are essential for cancer cell survival. As cancer is a heterogeneous disease with multiple aberrant signaling pathways, inhibiting these targets simultaneously may be an effective therapy for gastric cancer.