A common diabetes drug could help treat cancer, based on its insulin, obesity links
Being too fat raises the risk of Type 2 diabetes. That’s common knowledge.
What is less well-known is that scientists have linked cancer to the same obesity-related metabolic abnormalities that drive diabetes — especially resistance to insulin, the hormone that enables cells to absorb blood sugar and turn it into energy.
Indeed, an American Cancer Society report published this week shows that while overall cancer rates have been falling for 25 years, partly because of less smoking, obesity-related cancer deaths are rising.
The biologic connections are complex and still unclear, but they fit with a hallmark of cancer that was recognized a century ago: Malignant cells thrive on sugar, or glucose. They take up much more glucose than healthy tissue.
Obese patients’ high blood sugar “may impact tumor growth by providing cancer cells with an abundance of fuel,” explains a review article co-authored by Ryan Dowling, a biochemist at Princess Margaret Cancer Center in Toronto.
Although the worldwide obesity epidemic makes this cancer link ominous, the evolving understanding of it suggests that targeting insulin resistance could have anticancer effects. That’s why metformin, the mainstay diabetes drug that reduces the liver’s release of glucose, is being investigated to help treat and even prevent cancer. Scores of clinical trials around the world are testing it in breast, bladder, lung, colon, gynecological and other malignancies.
“I don’t think anybody expects that metformin will have a drastic or long-term effect on cancer by itself,” said Fox Chase Cancer Center oncologist Daniel Geynisman, who is conducting a trial of metformin in prostate cancer that has come back after conventional treatment. “The question is, can it augment our standards of care — not to mention helping with” insulin resistance.
Metformin also has the plus of being a well-tolerated, inexpensive, generic drug.
“It costs pennies a day,” said Dowling in Toronto. “If it were to work, it would be a massive bonus.”
Starting 50 years ago, population-based studies found that diabetes increased the risk of numerous types of cancer, and worsened the outlook. But an “association,” as scientists call it, just raises a red flag.
“A critical question is whether the associations between diabetes and the risk of certain cancers is largely due to shared risk factors (obesity, poor diet, physical inactivity and aging), or whether ... the metabolic derangements typical of diabetes increase the risk for some types of cancer,” the American Cancer Society and American Diabetes Association wrote in a 2010 joint report on diabetes and cancer.
Researchers are still deciphering the answer. Studies in cells and animals show that signaling proteins secreted by fat, called adipokines, are altered in obesity and sometimes overstimulate cancer cells. Chronic inflammation and sex hormones also seem to contribute to the interplay of obesity and cancer. But insulin, produced by the pancreas to regulate blood sugar, is most consistently implicated as a culprit in cancer development and outcomes.
Many types of cancer cells grown in lab dishes, particularly breast cancer cells, produce an abundance of protein “receptors” that receive signals from insulin and a closely related hormone called insulinlike growth factor. This signaling network helps malignant cells get and use glucose, and may activate pathways that drive cancer cell growth, proliferation, survival, and metastasis, the deadly spread to distant tissues.
“It also appears that insulin (signaling) may stimulate normal cells that are involved in cancer progression,” such as smooth muscle cells that form new blood vessels needed by tumors, said the ADA/ACA joint report.
Ongoing trials in less formidable cancers are expected to reveal whether metformin has benefits — and survival is not the only measure. Some studies are also looking at weight loss, metabolic factors, cardiovascular disease, and quality of life.