Researchers are likely to have uncovered a novel mechanism behind the ability of the common diabetes drug metformin to inhibit the progression of pancreatic cancer.
Diabetic patients taking metformin have a reduced risk of developing pancreatic cancer. Among patients who develop the tumour, those taking the drug may have a reduced risk of death, the study revealed.
Metformin — a commonly used generic medication for type 2 diabetes — decreases the inflammation and fibrosis characteristic of the most common form of pancreatic cancer, the researchers said.
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This beneficial effect may be most prevalent in overweight and obese patients, the findings indicated.
“We found that metformin alleviates desmoplasia — an accumulation of dense connective tissue and tumour-associated immune cells that is a hallmark of pancreatic cancer,” said lead author Dai Fukumura — associate professor of radiation oncology at Harvard Medical School in Massachusetts, US.
The study focused on pancreatic ductal adenocarcinoma — the most common form of pancreatic cancer — which also accounts for almost 40,000 cancer deaths in the US ever year. Half of those diagnosed with this form of pancreatic cancer are overweight or obese, and up to 80 per cent have type 2 diabetes or are insulin resistant, said the researchers.
The researchers first found that levels of hyaluronan — a component of the extracellular matrix — were 30 per cent lower in tumour samples from overweight or obese patients who were taking metformin to treat diabetes than in those who did not take the drug. In obese mouse models, the researchers found that metformin treatment reduced levels of tumour-associated macrophages by 60 per cent and reduced expression of genes involved in remodeling the extracellular matrix of tumour tissue.
“Understanding the mechanism behind metformin’s effects on pancreatic and other cancers may help us identify biomarkers — such as patient body weight and increased tumour fibrosis — that can identify the patients for whom metformin treatment would be most beneficial,” the authors noted in a study published in the journal PLOS One.