Omental fat-mediated chemoresistance to gastric cancer originating metastases

Omental spread is common in gastric adenocarcinoma, representing an advanced stage that harbors poor prognosis mostly due to resistance to systemic therapy. We have shown previously that factors secreted by fresh human omental-fat specimens induce chemoresistance of gastric cancer cells. In this project, we will further characterize the effects that omental-fat secreted factors have on the chemoresistance of gastric cancer. In vitro co-culture system will be used to systematically assay the effect of the different omental-fat secreted factors on chemoresistance. In addition, FPLC/MS and secretome library screening will be used to find relevant factors that can confer resistance. Next, we will explore omentum-mediated resistance mechanisms with in vitro and vivo studies. Finally, the clinical implications of blocking selected secreted factors on drug treatment efficacy will be tested using PDX mice models.