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The diabetes-cancer link

David Potter, M.D., Ph.D., is exploring whether a drug used to treat diabetes can also help prevent breast tumors from forming. (Photo: Scott Streble)

University researchers delve deeper into the connection

It has been more than a decade since evidence first emerged linking diabetes to cancer, and what doctors have learned so far is grim: Diabetics are twice as likely to get cancer of the liver, uterus, and pancreas, and they are 20 to 50 percent more likely to develop colon and breast cancer. Women who have breast cancer are almost 50 percent more likely to die if they also have diabetes.

“There’s definitely a proven connection between diabetes and cancer,” says David Potter, M.D., Ph.D., a breast cancer physician and member of the Masonic Cancer Center, University of Minnesota. “But even though we’ve learned a lot, there’s much more work to be done to get us to workable solutions to reduce cancer risk for diabetic patients.”

Potter is currently exploring whether the drug metformin, which is used to treat diabetes, may also keep breast tumors from developing. He hopes that his study, funded by a grant from the Randy Shaver Cancer Research and Community Fund, will shed more light on the potential of metformin as a breast cancer treatment.

Like Potter, Masonic Cancer Center member Margot Cleary, Ph.D., is intrigued by recent evidence that people with type 2 diabetes who are being treated with metformin seem to have a reduced breast cancer rate. She’s also studying the medication.

“I’m not a cancer person,” says Cleary, a professor at the University’s Hormel Institute in Austin, Minn. “I’m a nutritionist. The springboard for my initial research was the connection between obesity and breast cancer. So in this study, we’re going to get two birds with one stone: We’ll look at how, or if, metformin impacts tumor development in obese mice, and we’ll compare those results to how calorie restriction impacts tumor development.”

Metformin is thought to act in a manner similar to calorie restriction, but the two interventions have not been directly compared, Cleary says.

Her team’s hypothesis? Obesity will accelerate the development of a tumor; restricted-calorie diet will delay the development of a tumor; and metformin will also delay the development of tumors. The group will be monitoring the mice closely to see whether metformin is more effective than calorie restriction in relationship to body weight.

“Metformin is quite nontoxic,” Cleary explains, “so if research can show it also has definite anticancer properties, and if we can identify women at high risk for breast cancer, we could offer them metformin to, hopefully, delay or even deter the development of a tumor.”

Deepali Sachdev, Ph.D., hopes that her research will lead to tests that help oncologists choose the best drug for each patient. (Photo: Scott Streble)

Deepali Sachdev, Ph.D., an assistant professor in the departments of Medicine and Pharmacology, comes at the cancer-diabetes problem from a completely different angle. Her group is looking closely at the role of insulin-like growth factors and insulin in breast cancer. Both are hormones that affect cells through the highly related insulin-like growth factor receptor and insulin receptor, which are crucial for controlling glucose levels.

“People with obesity, with high levels of insulin, can have higher incidence of breast cancer,” Sachdev says. “And insulin and insulin receptors definitely affect breast cancer growth and metastases.”

Scientists already know that these two receptors can be present in tumor cells in various combinations, and drugs targeting the receptors are being explored through clinical research. To ensure the successful development of these drugs, however, researchers need to know which combinations of these receptors are present in a person’s tumor.

Enter Sachdev and her team, whose first step was to see if they could get good images of cancer cells in lungs—a challenge because MRI traditionally has not been very effective with lung imaging.

But Sachdev knew she could find some of the world’s top imaging experts just across campus.

“We worked with Michael Garwood [Ph.D.] at the Center for Magnetic Resonance Research, and his group developed an MRI method to get very good images of the lung,” she says, citing support from the Prospect Creek Foundation. “We were able to clearly show breast tumor cells that had metastasized to the lung. So step one was successful.”

Now Sachdev is in what she calls the “biology phase” of the study, working to combine a special nanoparticle with a molecule that will allow the nanoparticles to home in on tumor cells expressing the insulin-like growth factor receptor.

“This will enhance the sensitivity of the imaging, allowing us to see the metastasized tumor cells that express the receptor,” she explains.

Sachdev hopes that, eventually, tests will be able to identify which combinations of these receptors are in a person’s tumor, allowing oncologists to choose the most effective drug for treatment.

The relationship between cancer and diabetes is complex, and University scientists are confident that the questions they’re out to answer will evolve.

“The timeline for study is forever!” Cleary says. “In a cancer-diabetes study, one answer always leads to another question. If the funding is there, then you move on to try and solve the next challenge.

“That’s the way the work gets done—one small step at a time.”

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