Some Diabetes drugs may help Cancer spread

Researchers have known that reactive oxygen species, or free radicals, can do serious damage to cells and trigger cancer. Antioxidants can neutralize those effects, although clinical trials on cancer prevention have yielded mixed results. Several recent studies have also suggested that antioxidants have a dark side. If cancer is already present, for example, they may fuel its proliferation. That, suspects Martin Bergö, a cancer biologist at the Karolinska Institute in Stockholm, is because although free radicals harm healthy cells, they can also be toxic to cells that are already cancerous. That means that the antioxidants that curb those free radicals can help cancer cells rather than hurting them. Last fall, Bergö’s group reported that ingestion of extra antioxidants drove the metastasis of melanoma in a mouse model, though they didn’t have any effect on the primary tumor.
A team led by molecular toxicologist Donna Zhang at the University of Arizona in Tucson has now taken a different tack. With colleagues in China, she focused on a protein called NRF2. It regulates a cellular defense response that helps protect cells from oxidative damage caused by environmental toxins or carcinogens. Although NRF2 has many benefits, loss of NRF2 regulation leads to high levels in certain cancer cells, such as some lung cancers, and it may help them migrate, Zhang says.
Some diabetes drugs just happen to activate NFR2. That’s an off-target effect, Zhang explains, that is secondary to the drugs’ ability to lower blood sugar. People with type 2 diabetes are already at a higher risk for cancer. So what to do with this information next “is a dilemma,” Zhang says, because so far there are no data suggesting that the drugs (saxagliptin and sitagliptin) promote metastasis in people with both diabetes and cancer. Zhang, for one, thinks that diabetes patients with cancer shouldn’t take medications that activate NRF2, just to be cautious.