Metformin as a Metabolic Therapeutic in Ovarian Cancer
In this research project, the Mayo Clinic Ovarian Cancer SPORE is collaborating on exploration of the mechanism by which metformin affects tumor cell growth and chemoresistance.
Independent retrospective analyses by investigators at the University of Chicago and Mayo Clinic have shown that administration of metformin, an oral biguanide prescribed for patients with diabetes to improve glycemic control, is associated with improved progression-free survival in patients who have diabetes and ovarian cancer compared with patients who have diabetes and ovarian cancer treated with other agents.
Subsequent in vitro studies using ovarian cancer cell lines and an organotypic 3D model of ovarian cancer metastasis suggest that metformin inhibits tumor growth, induces apoptosis and sensitizes tumor cells to platinum-paclitaxel chemotherapy by modifying ovarian cancer cell metabolism.
Investigators in this project propose to:
- Identify the mechanisms by which metformin affects tumor cell growth and chemoresistance, focusing on both tumor and stromal cells
- Use patient-derived ovarian cancer xenografts to study pharmacodynamic markers of metformin action
- Use prospectively collected serum and tissue samples from a randomized phase II clinical trial of standard therapy with or without metformin, including paired samples from patients treated in the neoadjuvant setting, to understand the mechanisms of metformin anti-neoplastic action in the clinical setting
The accompanying clinical trial is the first clinical trial to examine the impact of metformin on standard ovarian cancer therapy (surgery and adjuvant or neoadjuvant chemotherapy) as part of initial therapy, a setting in which investigators hypothesize metformin will have the largest impact.