Metformin as a Metabolic Therapeutic in Ovarian Cancer
Administration of metformin, an oral biguanide prescribed for patients with diabetes to improve glycemic control, was shown in independent retrospective analyses by investigators at the University of Chicago and Mayo Clinic to be associated with improved progression-free survival of patients with diabetes and ovarian cancer compared to patients with diabetes and ovarian cancer treated with other agents.
Subsequent in vitro studies using ovarian cancer cell lines and an organotypic 3-D 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 Ovarian Cancer SPORE project propose to:
- Elucidate 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 plus or minus 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.
This research project on metformin is being led by investigators at the University of Chicago who are collaborating with Mayo Clinic researchers on the Ovarian Cancer SPORE:
- Ernst Lengyel, M.D., Ph.D.
- Iris Romero, M.D.
- Gini Fleming, M.D.
Co-investigators on this project are: