A new method uses a portion of a naturally occurring protein inhibitor of angiogenesis to reduce the formation of new blood vessels that tumors need to grow and simultaneously improve drug delivery. The research was published in The FASEB Journal (2015; doi:10.1096/fj.14-261636).
The protein inhibitor of angiogenesis is called thrombospondin-1 (TSP-1). The portion, known as 3TSR, interacts with the protein CD36 and causes endothelial cells, which are needed for tumors to create new blood vessels, to stop growing and die. In turn, this reduces the formation of new blood vessels needed for tumors to grow.
“We hope that this study will lead to novel treatment approaches for women diagnosed with advanced stage ovarian cancer,” said Jim Petrik, PhD, a researcher involved in the work from the Department of Biomedical Sciences at the University of Guelph in Guelph, Ontario, Canada.
“The use of anti-angiogenic therapy, combined with metronomic chemotherapy, has the potential to significantly improve our ability to treat advanced stage ovarian cancer while simultaneously reducing the treatment effects for women diagnosed with this disease.”
To make the discovery, Petrik and colleagues injected mouse ovarian cancer cells into the ovaries of mice. The resulting tumors were allowed to grow until they were similar to those in patients with advanced ovarian cancer, including the spread of small tumors throughout the abdomen.
Pretreatment with 3TSR improved chemotherapy drug delivery. When the pretreatment was combined with low-dose chemotherapy, it resulted in the most significant tumor regression and survival. This approach caused tumor shrinkage and resulted in destruction of abnormal, dysfunctional tumor blood vessels. The result was a smaller tumor, with improved blood supply.
Then, researchers could exploit this enhanced blood supply to improve chemotherapy drug delivery to the tumor and were able to treat with very small amounts of drug, with excellent clinical effect.