Metformin investigated further for anti-cancer effects

A new study published in The Laryngoscope sheds new light on the relationship between the diabetes drug metformin and the biology of cancer cells.

Several recent studies have shown that diabetic patients with head and neck cancer who take metformin have had better outcomes than those without diabetes, so investigators at The Sidney Kimmel Cancer Center at Thomas Jefferson University tested tumor cells before and after metformin treatment in patients without diabetes.

“This study is the first step in showing how metformin acts on head-and-neck tumors,” said senior author Ubaldo Martinez-Outschoorn, MD, assistant professor in the Department of Medical Oncology at Thomas Jefferson University, Philadelphia, PA, and researcher at the Sidney Kimmel Cancer Center, Philadelphia. “We are excited that it could eventually offer patients a method of improving their outcomes with few side effects.”

Researchers administered metformin to 39 patients without diabetes and examined their tumor samples before and after treatment. The doses of metformin were approximately half of the short-term doses administered to patients with diabetes.

Dr. Martinez-Outschoorn’s team showed that metformin alters the cancer microenvironment and changes the pathways that cancer cells rely on for growth.

“Tumors need a lot of energy to grow quickly, so throwing a wrench in their energy-production pathway makes this kind of cancer more susceptible to standard therapies,” according to first author Joseph Curry, MD, associate professor in the Department of Otolaryngology at Jefferson.

The patients who received metformin had a significant increase in tumor cell apoptosis. The cancer-supporting fibroblasts also showed signs of deterioration, indicating that the cells were less capable of helping neighboring cancer cells grow and metastasize to other parts of the body.

“This study demonstrates that metformin has effects on head-and-neck cancers, at safe doses, that are at or lower than what is given to diabetic patients and that it changes head-and-neck tumor biology in a way that likely makes the cancer easier to kill,” said co-author Madalina Tuluc, MD, PhD, associate professor and director of surgical pathology in the Department of Pathology, Anatomy and Cell Biology at Jefferson. “Metformin disrupts the cancer’s most efficient method of generating fuel for its growth and shuts off the cancer’s support system.”

Other work suggests that metformin could have immunotherapeutic effects on tumors as well.

“The next step would be to test these doses of metformin in phase II clinical trials with a greater number of patients,” said Dr. Martinez-Outschoorn.

Metformin is well tolerated and has a long track record of being a safe medication. In this study, few patients experienced side effects from metformin. Those that were reported were considered low-grade.