Characterization of the Bi-directional Cross Talk Between Cancer Cells and Carcinoma-associated Fibroblasts

In the past several decades, there has been limited progress in the treatment of ovarian cancer (OvCa) and it remains the most lethal of all gynecologic malignancies. As is the case with most solid tumors, metastasis is the primary contributor to mortality. When OvCa metastasizes, it most often homes to regions within the abdominal cavity like the omentum, a 15x15x3 cm large fat pad within the peritoneal cavity that is rich in stromal cell types including mesothelial cells, adipocytes, and fibroblasts. Once OvCa colonizes in the omentum, the environment shifts to one which supports the growth of OvCa. Eventually, the entire omentum is transformed into solid tumor, which causes grave complications, compressing surrounding organs and causing a bowel obstruction. We believe that the interaction between OvCa and the stromal cell types is key to the progression of this deadly disease.

This study will use an innovative, systematic approach to discover the signaling changes which occur intracellularly with the interaction of OvCa cells and a crucial stromal component, carcinoma-associated fibroblasts. Once we determine the key signaling pathways, our findings can be used to identify new therapeutic targets for the treatment of ovarian cancer. Indeed, discovery of key
signaling pathways in other cancers, such as Her2/neu in breast cancer, has led to significant advances in treatment.