Scientists at Ohio State University Medical Center are testing a popular drug used in the treatment of diabetes to see if it might be a non-toxic option to slow the development of breast cancer.

The drug, rosiglitazone, is frequently prescribed for type II diabetes mellitus. Rosiglitazone decreases insulin resistance by helping the body use the insulin it produces more effectively. People who are insulin resistant are not able to utilize the insulin they make, so sugar builds up in the blood, often leading to type II diabetes.

But cancer researchers are interested in rosiglitazone for some of its other properties.

"One of the things that is so intriguing about rosiglitazone is that it also appears to slow the growth of certain kinds of tumors," says Dr. Lisa Yee, a surgical oncologist at The Ohio State University Medical Center.

Yee says rosiglitazone - also known as Avandia - activates a cell receptor known as PPARg, a player in a family of receptors that includes the more commonly known estrogen and progesterone receptors.

"We are interested in drugs like rosiglitazone because activation of PPARg appears to be able to inhibit the growth of breast cancer cells and cause tumor cell death," says Yee.

Yee and her colleagues will be offering rosiglitazone to women with small breast cancers in a Phase I study to check for side effects. Patients in the trial will take rosiglitazone for anywhere from 2-6 weeks before surgery, while researchers measure several factors in the breast cancer tissue both pre- and post-treatment.

Yee and her colleague Dr. Charis Eng will be looking for several things, including the presence of proteins found during cell growth and the presence of genetic mutations that might signal an individual's resistance to the drug. Additionally, they will be assessing the drug's impact on how the tumor cells look and whether the treated patient's cancer cells return to a more normal appearance.

"We are just beginning to understand the function of PPARg," says Yee. "We know from a variety of laboratory studies that this receptor affects inflammation, angiogenesis or the development of blood vessels, and immune system function in addition to its effects on tumor growth and differentiation. We need to know more about how this all works in cancer patients." She says the approach may lead to an intervention for breast cancer that is easily tolerated and effective for women whose breast cancers are either positive or negative for progesterone or estrogen receptors.

Yee's work on PPARg and breast cancer could also lead to further understanding about any link between dietary fat and the development of cancer. "In addition to drugs like rosiglitazone, there are natural activators of PPARg such as certain fatty acids and fatty acid by-products. The whole question of the relationship between dietary fat and cancer is complex and difficult to study, but PPARg may play a role in this interaction," says Yee.

SOURCE:
Ohio State University Medical Center (http://www.osumedcenter.edu)