Written and posted by : Bhawana Jain
Published on: January 26, 2017
Article Source: Thomas Jefferson University
Abstract: To understand the effect of Metformin (a diabetes drug) on cancer cells, researchers have examined cancer cells before and after Metformin treatment in non-diabetic cancer patients. The research found that Metformin disrupts the way by which cancer cells produce energy for their growth thus shutting off its support system.
Last few years of research has shown that diabetic patients with head and neck cancer might have better results as compared to non-diabetic patients when they take the drug metformin for their diabetes. To understand the relationship between metformin and the biology of cancer cells, researchers at the Sidney Kimmel Cancer Center at Thomas Jefferson University examined tumor cells before and after metformin treatment in non-diabetic cancer patients. Their pilot clinical trial results have been published in the journal The Laryngoscope.
“This study is the first step in showing how metformin acts on head-and-neck tumors, and we are excited that it could eventually offer patients a method of improving their outcomes with few side effects,” says senior author Ubaldo Martinez-Outschoorn, M.D., Assistant Professor in the Department of Medical Oncology at Thomas Jefferson University and researcher at the Sidney Kimmel Cancer Center.
The researchers showed that metformin not only disrupts the pathways that cancer cells utilize to produce fuel for growth, but also changes the cancer microenvironment, the cells that surround and support the tumor. “Because tumors need a lot of energy to grow quickly, throwing a wrench in their energy-production pathway makes this kind of cancer more susceptible to standard therapies,” says first author Joseph Curry, M.D., Associate Professor in the Department of Otolaryngology at Jefferson.
The research involved treating 39 patients with metformin and testing their tumor samples before and after metformin treatment. Only a half of the actual dose of metformin which diabetic patients take were given to the subjects for a small duration of time. Then, researchers looked at molecular markers of cell death, or apoptosis, and alterations in metabolic pathways that might make the cancer more susceptible to standard therapy. The non-diabetic subjects treated with metformin showed a significant increase in tumor cell apoptosis. Not only this, the cells surrounding the tumor, the so called cancer-supporting fibroblasts, also displayed marks of damage showing that the cells were less capable of helping neighboring cancer cells grow and metastasize to other parts of the body.
Metformin has shown a high track record as a safe medication and is much less toxic that traditional cancer treatments. In this research, only some patients had side effects from metformin and those that were reported were considered low grade such as gastrointestinal upset. None of the patients faced high grade adverse events.
“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,” says study co-author Madalina Tuluc, M.D., Ph.D., an 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.” In addition, 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,” says Dr. Martinez-Outschoorn.
Joseph Curry et al. Metformin effects on head and neck squamous carcinoma microenvironment: window of opportunity trial. The Laryngoscope, January 2017 DOI: 10.002/lary.26488