Researchers are a step closer to figuring out how metformin may help prevent cancer.
Metformin is generally used to treat type 2 diabetes. The drug helps the body use insulin more effectively.
It also helps lower glucose production in the liver. And it’s relatively inexpensive.
Observational studies have suggested that people who take it may have a lower risk of certain types of cancer.
Researchers at the University of California, San Diego, wanted to know why. The answer could lead to better prevention and more effective cancer treatment.
Details of their research are published in the journal eLife.
What the research says
All cells possess cell polarity. It’s what allows them to perform specific tasks.
Polarity lets epithelial cells form protective walls in cavities and organs. The walls protect against toxins, pathogens, and inflammatory triggers.
Any crack in the wall can open the door to cancer.
The research team identified the mechanism that helps keep the wall strong.
Researchers already knew about something called the stress-polarity pathway.
As stated in the researchers’ press release, it’s “a specialized pathway mobilized only during periods of stress. It is orchestrated by a protein kinase called AMPK that protects cellular polarity when epithelial cells are under energetic stress and an activator of AMPK called LBK1.”
LBK1 is a tumor suppressor. LBK1 mutations are associated with loss of cell polarity and cancer.
The mystery was in how the LKB1-AMPK pathway preserves cell polarity during stress.
The new research found that the stress-polarity pathway relies on a protein called GIV/Girdin. Metformin affects this protein.
"In summary, by identifying GIV/Girdin as a key layer within the stress-polarity pathway we've peeled another layer of the proverbial onion," Dr. Pradipta Ghosh, the study’s senior author, said in the press release.
Ghosh explained that the research provided new insights into the epithelium-protecting and tumor-suppressive actions of metformin.
Cancer fighting properties
Dr. Timothy Byun is a medical oncologist with the Center for Cancer Prevention and Treatment at St. Joseph Hospital in Southern California.
He told Healthline that metformin has several mechanisms that may contribute to its anticancer property.
Byun said multiple epidemiologic studies show an association between metformin use and reduced cancer incidence and mortality.
“It's also well-known that individuals with diabetes or metabolic syndromes have increased insulin production or insulin-resistance state. Hyperinsulin state is associated with increased risk of certain cancers,” said Byun.
He explained that metformin has insulin-lowering activity. This may slow cancer in hyperinsulinemic patients.
It also suppresses production of adenosine triphosphate (ATP). ATP transports energy within cells.
By suppressing it, cancer cells have less energy available. This makes it harder for cancer cells to spread or survive.
“Population studies suggest cancer incidence reduction of 14 to 40 percent. And mortality reduction. The main sites appear to be in breast, colon, liver, pancreas, endometrium, and lung,” said Byun.
The cancer-nutrition connection
“It’s exciting, if you think about it,” said medical oncologist Dr. Jack Jacoub in an interview with Healthline.
“There’s an increasingly loud voice about how important nutrition might be in cancer. In fact, it could become one of the tools we use to treat it,” explained Jacoub, director of thoracic oncology at MemorialCare Cancer Institute at Orange Coast Memorial Medical Center in California.
“There’s been some skepticism in the field,” he added. “This is part of a new area of looking at prevention and treatment related to glucose and insulin. Also, cholesterol, triglycerides, and other pathways that affect cancer cells.”
Jacoub said nutrition, weight control, and level of activity all matter. All affect development, progression, and response to therapy.
“Metformin is part of a growing story. It would be irresponsible to say metformin is the standard of care at this point. It’s early in the research. But if you’re already on it for diabetes, there may be a lot of benefits to you beyond controlling sugar,” advised Jacoub.
Will metformin eventually help prevent or treat cancer?
It’s too soon to say.
“Researchers have been looking at metformin for several years,” said Jacoub. “There are unique features in terms of risk factors of specific cancers. Maybe a drug like metformin could impact cancer cells of that group. There are ongoing trials involving women with a history of breast cancer to learn if it could reduce the risk of recurrence. It’s a well-established concept in breast cancer. There’s a very large trial going on specifically asking that question.”
Byun suggested that phase III studies may be able to determine if metformin is effective in prevention or decreasing recurrence. Or if it could make chemotherapy or radiation therapy more effective.
There’s no immediate role for metformin in treating cancer, according to Byun. He would like to see positive phase III study data before changing his pattern of practice.
“There is a phase III study in France looking at hepatocellular cancer risk in patients with viral hepatitis C cirrhosis. [Cirrhotic patients are at high risk of developing liver cancer due to underlying liver damage.] This study randomizes patients on metformin vs. placebo for three years,” he said. “Another phase III study is in prostate cancer [and patients with] localized disease who are undergoing active surveillance, rather than definitive surgery or radiation therapy. It is looking at time to disease progression.”
“These efforts are underway. But it will take some time for us to know,” said Byun.