Research field buzzing with interest about positive effects of metformin on cancer

EASD 47th Annual Meeting

LISBON — As more data become available, excitement continues to build about the possible links between metformin and cancer.

“This is a complex area of research, and many teams are investigating this topic around the world,” Michael Pollak, MD, professor of oncology at McGill University and director of the Cancer Prevention Center at the Jewish General Hospital, Montreal, said here.

Available evidence clearly shows an increased risk for certain cancers, such as liver, colon and pancreas, among people who have type 2 diabetes. Similarly, there is also evidence that hormonal changes in type 2 diabetes may raise cancer risk, such as high levels of insulin and increased inflammatory cytokines. Now, recent evidence suggests that metformin, an inexpensive and frequently used diabetes drug, may reduce the risk for certain cancers.

Two speakers here discussed the current research on metformin in cancer cells and the future of this exciting field of research.

Multiple actions of metformin on cancer cells

Frédéric Bost, PhD, of INSERM U895 in Nice, France, said there are more than 20 ongoing trials using metformin in cancer research, according to those registered on the NIH’s clinicaltrials.gov.

Edwin A.M. Gale

“In the next couple of years, the results of the numerous ongoing clinical trials should help to determine how to use metformin in cancer therapy,” Bost said in a press release.

At the molecular level, metformin activates the AMP-activated kinase (AMPK), a kinase regulated by the liver kinase B1 (LKB1), a tumor suppressor gene. AMPK activation inhibits the mammalian target of rapamycin (mTOR), which controls protein synthesis and cell proliferation. This leads to the hypothesis that metformin could affect tumor growth and reduce the risk for various cancers, according to Bost.

Several recent studies, including pioneer research by Evans et al, have demonstrated that metformin decreases the incidence of cancer in patients with diabetes. Additionally, concordant studies have revealed that metformin exerts antineoplastic effects in cancer cells and in animal models. If one of the direct benefits from metformin is a decrease in insulin, cellular studies show that the drug can also directly affect cancer cell proliferation and the AMPK/mTOR axis.

An oncologist’s point of view

Retrospective follow-up studies of medications in use occasionally reveal information that causes concern, such as previously unrecognized toxicities or increases in cancer risk. The opposite has happened with metformin: recent studies imply an unexpected reduction in cancer risk associated with use of this drug, Pollak said during a press conference.

As an oncologist, Pollak and his research team have studied the influence of diabetes and diabetes treatments on various cancers at the level of population studies, experimental models and also clinical research.

“This is a young and active research field, and while there has been considerable progress more work needs to be done before definitive conclusions will be available.

“However, as metformin is off-patent, the research efforts are not centrally coordinated, as is the case when the pharmaceutical industry discovers and patents any new molecule. One important topic of investigation concerns the possibility that metformin may be useful for cancer treatment or prevention even among people without diabetes,” Pollak stated in a press release.

A complex relationship between diabetes, cancer

For Pollak, “it is reflecting how the fields of diabetes research and cancer research are converging in many ways.”

Edwin A.M. Gale, MD, current editor of Diabetologia, said, therapies aside, the basic relationship between diabetes and cancer continued to be closely studied. It is known that obesity is one of the major acquired risk factors for cancer, and researchers are looking at other confounding factors such as insulin resistance, inflammation and other obesity-related factors.

“Cancer has overtaken cardiovascular disease as the leading cause of death in the general population up to age 65,” Gale said. “This is the future for diabetes. Cancer is now part of the diabetes spectrum. The better we get at managing heart disease, more of our patients are going to be dying from cancer. Therefore, cancer management is becoming central to what we do in diabetes.” – by Katie Kalvaitis

For more information:

• Bost F. The multiple biological actions of metformin on cancer cells.
• Gale EAM. The dread diagnosis: Carcinoma of the pancreas and diabetes.
• Pollak M. How diabetes and diabetes treatments influence cancer risk: 2011 update. Presented at: The European Association for the Study of Diabetes 47th Annual Meeting; Sept. 12-16, 2011; Lisbon.

Disclosures: Drs. Bost and Gale report no relevant financial disclosures. Dr. Pollak consults for Novo-Nordisk and has in the past consulted for Pfizer and Sanofi Aventis.

Ulf Smith

Type 2 diabetes has an increased risk for certain cancers. This, of course, has been partly due to the fact that patients with type 2 diabetes also have obesity, and obesity is a well-known risk factor for certain types of cancer. The explosion of interest, in addition to the problem of obesity, has been on specific factors related to diabetes and other factors related to how we treat diabetes that can increase or decrease the risk for cancer. The purpose of this session is to give an update on where we stand and also to discuss mechanisms for what we hope to be a protective effect by metformin, which is the first-line therapy that has been around for more than 30 years.

– Ulf Smith, MD, PhD
President
European Association for the Study of Diabetes

Disclosure: Dr. Smith reports no relevant financial disclosures.

In the last 3 years, the profile of this [association] has gone upwards. We have this problem of detection bias, where sub-cancers are detected around the time of diabetes diagnosis and cancers are co-detected in the clinic within the first few months most cancers are diagnosed. An individual goes from a level of no health provider contact to a high level.

This topic is now very much on the radar of not only the European diabetes community but also firmly on the radar of the European Cancer Organization and the European Association for the Study of Obesity. There have been parallel symposia and special sessions [on this issue] at their respective meetings this year.

– Andrew G. Renehan, PhD
Clinical Senior Lecturer/Honorary Consultant
University of Manchester School of Medicine, UK

Disclosure: Dr. Renehan has received honoraria for lectures with Novo Nordisk.

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