Diabetes Drug Fights Cancer

Four new studies indicate that metformin, the medication most commonly used to control Type 2 diabetes for more than two decades, is an effective weapon in the fight against cancer. In the first study, published in Cancer Prevention Research, scientists induced premalignant conditions in mice and then gave them metformin. The anti-diabetes drug inhibited a protein called mTORC1 that researchers know contributes to oral cancers. Metformin reduced the size and number of oral tumors and significantly reduced the development of squamous cell cancers by 70 to 90 percent. “We clearly saw a direct effect on premalignant lesions,” said Silvio Gutkind, chief of the Oral and Pharyngeal Cancer Branch of the National Institute of Dental and Craniofacial Research at the National Institutes of Health. The second study, also published in Cancer Prevention Research, found that patients who have deadly pancreatic cancer and are prescribed metformin appear to have improved survival rates. In a study of 302 patients with diabetes and pancreatic cancer, 117 were prescribed metformin. After one year, 63.9 percent of the patients prescribed metformin were still alive, while only 46.3 percent of the group not prescribed metformin survived. By two years, 30.1 percent of the metformin group remained alive compared with 15.4 percent of the non-metformin group. Median survival was 15.2 months for patients prescribed metformin, and 11.1 months for patients not prescribed metformin. Those prescribed metformin had a 32 percent reduced risk for death. The third study, presented at the American Association for Cancer Research's annual meeting, showed that metformin slowed the growth of prostate tumors. Canadian researchers studied 22 men with prostate cancer who were scheduled to have their cancerous prostates removed. Before surgery, some of the men took 500 mg of metformin three times a day for an average of 41 days. Researchers found that the tumors grew more slowly in the men who took metformin. The fourth study, published in Cancer Discovery, looked at the effect of metformin on two common genetic mutations — BRAF and NRAS — of melanoma, the most deadly form of skin cancer. When metformin was combined with anticancer drugs such as axitinib that inhibit levels of VEGF-A, a molecule that promotes the formation of blood vessels and increases tumor growth, tumor growth decreased. Using meformin alone, tumor growth increased by twofold. But when metformin was combined with axitinib, tumor growth was suppressed by 45 percent. When it was combined with the anticancer drug bevacizumab, tumor growth was suppressed by 64 percent compared with 34 percent for bevacizumab alone. "We wish to initiate a clinical trial testing the combination of metformin and VEGF-A inhibitors in patients with BRAF-mutant melanoma, with the hope that this becomes an effective treatment option for people suffering from this deadly disease," said Richard Marais, professor of molecular oncology and director at The Paterson Institute for Cancer Research in Manchester, England. The metformin/anti-cancer connection goes back to 2005 when British researchers found that diabetics who took metformin (originally marketed as Glucophage) lowered their risk of developing cancer by 40 percent when compared to those taking other diabetic drugs. Additional studies have confirmed the initial findings. A clinical trial published in Cancer Prevention Research indicated that taking low-dose metformin for only 30 days suppressed the development of precancerous colorectal lesions in humans. An animal study implied that the drug reduced the number of tobacco-induced lung cancers by up to 73 percent. While scientists debate exactly how metformin fights cancer, a Canadian study released in January found that it protects cells from DNA damage that can lead to cancer. "This is a very safe agent and has been around for a while," Dr. Scott Lippman, chair of thoracic head and neck medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston, said at a news conference. "If someone had just synthesized metformin in a cancer lab, it would be considered a very important scientific development in the context of oncology," Dr. Michael Pollack of McGill University in Montreal told reporters attending a 2010 session of the European Association for the Study of Diabetes.