Title: Genomic analysis of ovarian cancer metastasis: towards improved understanding and treatment
It is widely acknowledged that the metastatic spread of cancer cells is responsible for most cancer related deaths. This is particularly true for ovarian cancer (OC) where the prospect of favorable outcome drops precipitously once cancer cells migrate beyond the confines of the primary tumor. Our laboratory is interested in using genomic approaches to better understand the molecular processes underlying OC metastasis and to develop novel therapeutic strategies to inhibit metastasis and improve patient outcome. Preliminary evidence suggests that OC metastases can be established from low frequency sub-clones present within the primary tumor resulting in significant genetic divergence between primary and metastatic tumors. Additional evidence indicates that the OC metastatic process involves epithelial-to-mesenchymal transition (EMT) with a concomitant reduction in the sensitivity of metastasizing cells to standard (platinum-based) chemotherapies. Ectopic over-expression of members of the miR-200 family of microRNAs is emerging as an effective strategy to reverse EMT and increase the sensitivity of metastatic OC cells to standard chemotherapies.