Avandia targeted as potential treatment against breast and ovarian cancer

A banned type 2 diabetes drug that prevents cancer cells from shielding against chemotherapy is being researched for use against breast and ovarian cancer.
Avandia is a thiazolidinedione (or glitazone) drug that has been used in the treatment of type 2 diabetes to reduce insulin resistance and improve insulin sensitivity. But in 2010 it was pulled from use as a diabetes treatment in the UK due to its association with an increased risk of heart attack and stroke.
Glitazones help the insulin that the body produces to work more effectively, but new research from Rice University suggests they also have a potential future use in cancer patients.
This is because the small molecules in Avandia can stop the production of glycoproteins, which are found in the protective mucus which lines the cells and organs of the human body.
Cancerous tumours manipulate these mucus cells to protect themselves from the immune system and chemotherapy.
Rice University bioscientist Daniel Carson said: “Cells of the immune system that kill tumours have to make contact with the cancer cell’s surface, but when they have these big barrier molecules on the surface, they’re protected.
“But tumors have learned a trick. Instead of keeping mucins on one end of a cell, where they would normally protect it from the external environment, they start putting mucins all over their surfaces.
“These mucins perform a very important protective function, lining your mouth, your glandular structures and your gastrointestinal tract, essentially acting like Teflon for those surfaces.”
The effects of rosiglitazone were studied on a glycoprotein known as MUC16 that protects breast and ovarian cancer cells. “MUC16 wound up being particularly interesting because it’s also known as CA125, which is the gold standard marker for ovarian cancer,” explained Carson.
“Women are routinely monitored for CA125 levels that normally are found at very low levels in serum. If you have certain tumors, these cancer cells begin to release fragments of CA125.”
When rosiglitazone was administered to cancer cells in a laboratory environment it led to glycoproteins being closed down. This occurred when the actions of cytokines, which trigger the protective response of the cells and increase MUC16 production, was disrupted.
Issues surrounding the drug need to be ironed out before it can be used in the fight against cancer as small doses used in the treatment of diabetes can actually increase the risk of cancer in people with diabetes. Researchers hope a way can be found to administer the drug safely in large enough doses to directly target tumours.
Carson added: “If you could shut down synthesis by 90 percent or more, which is achievable with these drugs, within two days you have enough reduction to remove the tumor’s protective coating.”
Their work will feature in the January issue of the Journal of Cellular Biochemistry.