Knowledge Bank

Fatty acid synthase (FAS), a 272 kDa protein complex regulated via the sterol regulatory binding element protein (SREBP) pathway, is implicated in intracellular de novo synthesis of fatty acids and is overexpressed in a variety of human epithelial tumors, including ovarian cancer. FAS demonstrates a role in mediating cellular proliferation, survival, and migration and invasion, while decreasing the rate of apoptosis within the cells, especially when upregulated. The goal of the present study is to investigate the role of FAS-mediated drug resistance in ovarian cancer cells. The results I have procured in recurrent ovarian cancer cell (ROCC) lines show a marked overexpression of FAS in human ovarian tumor samples and resistant ovarian cancer cell lines to be correlated with decreased apoptosis and increased cell migration. In addition, the FAS inhibitor cerulenin, in combination with cisplatin, causes significant induction of apoptosis and migratory inhibition in drug-resistant ovarian cancer cells. Therefore, I hypothesize that a mechanism by which ovarian cancer cells develop drug resistance is by upregulating the FAS pathway, allowing the increased metabolic demands of the cancer cells to be met. This pilot study suggests that targeting molecular FAS using a small molecule inhibitor may have therapeutic potential for treating drug-resistant ovarian cancer.