Results from current studies in mice may result in new therapies for a subset of human cancers that tend to be aggressive and resistant to existing treatments. Craig B. Thompson, MD, Director of the Abramson Cancer Center and Chairman and Professor of Cancer Biology and Medicine at the University of Pennsylvania and his team have been accumulating evidence over the last several years that p53, best known as a regulator of cell division, controls several metabolic pathways in cells. For potential cancer therapies, that means a drug that affects pathways controlled by p53 could help control p53-deficient tumours.
Significantly, the regulation of metabolic pathways by p53 is also influenced by metformin, the most widely used diabetes drug. Metformin activates the metabolic enzyme AMPK (AMP activated protein kinase), which exerts changes on cellular metabolism by affecting p53 function. Two observational studies already show that diabetic patients who take metformin have a lower rate of cancer diagnosis and mortality than other diabetics.
Thompson’s group injected human colon cancer cells that have normal p53 function into one side of mice and colon cancer cells that lack p53 into the other side. Four days later they started treating the animals with a daily injection of either a saline control solution or with metformin, using a dose comparable to diabetic treatment in humans.
Four weeks later, the p53-deficient tumours in mice treated with metformin were half the size of the p53 deficient tumours in control mice. There was no difference in the size of the p53 normal tumours between the animals treated with metformin or saline. They concluded that metformin slowed the growth of the colon cancer cells that lack a normal p53 function.
If preclinical tests continue to look promising, development of metformin as a cancer therapy may move quickly as the drug is already approved by U.S. Food and Drug Administration for use in humans, the researchers surmise.
MEDICA.de; Source: University of Pennsylvania