How metformin inhibits pancreatic cancer progression
January 18 2016
A report published on December 7, 2015 in the journal PLOS One reveals the discovery of researchers at Massachusetts General Hospital of a mechanism supporting metformin's ability to reduce pancreatic cancer progression. Earlier research has documented a lower risk of pancreatic cancer in diabetics treated with metformin, as well as a reduced risk of mortality among those who develop the disease.
Dai Fukumura, MD, PhD, of Massachusetts General's Department of Radiation Oncology and colleagues examined the most common form of pancreatic cancer known as pancreatic ductal carcinoma, which is associated with type 2 diabetes and insulin resistance. Among inital findings was a 30% lower level of hyaluronan in the tumor extracellular matrix of pancreatic cancer tissue derived from overweight and obese patients treated with metformin in comparison with samples from those who had not been prescribed the drug. "We found that metformin alleviates desmoplasia - an accumulation of dense connective tissue and tumor-associated immune cells that is a hallmark of pancreatic cancer - by inhibiting the activation of the pancreatic stellate cells that produce the extracellular matrix and by reprogramming immune cells to reduce inflammation," Dr Fukumura explained. "We also found these effects only evident in tumors from overweight or obese individuals, who appear to have tumors with increased fibrosis."
"Nearly 200 clinical trials are currently underway investigating the effect of metformin on tumors in both diabetic and nondiabetic patients," noted co-senior author Rakesh K. Jain, PhD, who is the director of the Steele Laboratory of Tumor Biology at Massachusetts Generals' Radiation Oncology Department. "Understanding the mechanism behind metformin's effects on pancreatic and other cancers may help us identify biomarkers - such as patient body weight and increased tumor fibrosis - that can identify the patients for whom metformin treatment would be most beneficial."
