How diabetes mainstay metformin may prevent tumors

Several observational studies have suggested that patients with diabetes who take the widely prescribed drug metformin may have a lower cancer risk than people who are not on the drug. But why?

Scientists at the University of California, San Diego, may be a step closer to answering that question. The researchers have identified a cellular mechanism by which metformin fortifies the epithelial cells that line body cavities and organs. By tightening up the junctions between those cells, the drug helps create a barrier against inflammation, toxins and other cancer-causing stresses, they believe. They published their findings in the journal eLife.

Metformin works by activating a cellular pathway called LKB1-AMPK, which shields “polarity,” or the ability of cells to carry out specialized tasks. The UCSD team discovered that a protein called GIV/Girdin is essential for metformin to be able to do that job. They demonstrated that the drug directs GIV toward the junctions in the epithelial layer, according to a press release from the university.

The UCSD team further demonstrated that when they took away GIV targeting and its activator, metformin, the beneficial effects of AMPK disappeared; the epithelial lining started to leak and eventually it collapsed.

Lead author and UCSD professor of medicine Pradipta Ghosh believes the team has “provided new insights into the epithelium-protecting and tumor-suppressive actions of one of the most widely prescribed drugs, metformin, which may inspire a fresh look and better designed studies to fully evaluate the benefits of this relatively cheap medication," she said in the release. Metformin has been on the market for more than 50 years for the treatment of Type 2 diabetes.

The UCSD study is one of many designed to unlock the mysteries behind metformin and its potential use beyond treating diabetes. Last year, researchers at the Albert Einstein College of Medicine in New York announced their plans for a trial called Targeting Aging with Metformin (TAME), during which patients with a range of diseases, including cancer, will be given the drug to see if it will fend off comorbidities.

And last December, startup Enlibrium raised $15 million in a Series A to develop compounds similar to metformin that they hope to prove will shrink tumors by depriving cancer cells of energy they need to grow. 

In their paper, Ghosh and her colleagues suggest that further studies of GIV expression in tumors would be warranted. Overexpression of the protein may help identify which cancer patients would be most likely to benefit from metformin, they say.