Metformin may inhibit the progression of pancreatic cancer by decreasing inflammation and fibrosis, a study published in PLOS One reported. 

About half of patients diagnosed with pancreatic ductal adenocarcinoma are overweight and obese; up to 80% have type 2 diabetes or are insulin resistant. Patients who take metformin are known to have a lower risk of developing pancreatic cancer. Further, patients who develop the tumor may have a reduced risk of mortality by taking metformin. 

Before this study, the mechanism of metformin against pancreatic cancer was not well established, as no potential biomarkers of response were reported. Study authors from Massachusetts General Hospital (MGH) evaluated cellular and animal models, and patient tumor samples, and found that this positive effect may actually be most prevalent in overweight and obese patients.

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In the study, metformin alleviated desmoplasia, a hallmark of pancreatic cancer where dense connective tissue and tumor-associated immune cells accumulate. Dai Fukumura, MD, PhD, the study’s co-senior author, explained that metformin worked “by inhibiting the activation of the pancreatic stellate cells that produce the extracellular matrix and by reprogramming immune cells to reduce inflammation.”

The team initially found that hyaluronan levels were 30% lower in tumor samples from overweight/obese patients taking metformin for their diabetes compared to those who did not take metformin. Obese animal models of pancreatic cancer that received metformin demonstrated lower levels of hyaluronan, collagen-1, and fewer activated pancreatic stellate cells (PSCs). Treatment with metformin lowered levels of tumor-associated macrophages by 60% and lowered expressions of genes related to the remodeling of the extracellular matrix of tumor tissue. Animals’ tumors treated with metformin also had reductions in a metastasis-associated change in epithelial to mesenchymal transition (EMT) and overall metastasis. 

A co-senior author of the study, Rakesh K. Jain, PhD, noted,” 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.” 

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