According to the American Cancer Society, up to 30 percent of all breast cancer patients are HER2/neu positive. This means they have too much of the HER2/neu growth-promoting protein, which causes the development of an aggressive form of breast cancer.
Although several drugs are available to treat HER2/neu producing breast cancer, such as Trastuzumab (Herceptin) or Lapatinib (Tykerb), effective prevention of this type of breast cancer remains a challenge. New findings from Xiaohe Yang, MD, PhD, associate professor with NC Central University’s Nutrition Research Program on the NC Research Campus (NCRC) in Kannapolis, point to a new mechanism for the prevention of HER2/neu producing breast cancer.
Yang studies cancer biology, experimental therapeutics and pre-clinical modeling of cancer using both cell culture and animal models. His success using animal models to research breast cancer inspired him to take a novel approach to the investigation of the drug metformin and its anti-tumor activity.
Metformin and HER2/neu Prevention
Metformin is a blockbuster drug for the treatment of type 2 diabetes. It lowers glucose or sugar in the blood by reducing the amount that can be absorbed from food and produced by the liver. Metformin also helps the body respond to insulin, the hormone made by the pancreas that helps the body absorb glucose.
Research is showing metformin may be effective in the treatment of other diseases. Diabetic patients taking metformin were suggested to have lower incidences of breast and other cancers compared to the general population. Many of the preclinical studies looking at the link between metformin and cancer were conducted using cancer cell lines, and did not, Yang explained, address how metformin interferes with the process of malignant transition in HER2/neu tumor development.
“The mechanism of metformin mediated anti-tumor activity is not clear,” he commented. “That is one thing. Another thing is that understanding this mechanism may lead to either better treatments or the prevention of HER2/neu breast cancer.”
With funding from a Research Scholars Grant from the American Cancer Society, Yang designed an experiment in mice genetically predisposed to developing HER2/neu to study how metformin prevents HER2/neu tumor development by targeting a specific population of cells known as tumor-initiating cells.
Recent advances suggest that cancers are originated from a special group of tumor cells called cancer stem cells. Targeting cancer stem cells is a promising approach for treating and preventing various cancers, including breast cancer.
“These tumor-initiating cells have cancer stem cell properties like indefinite proliferation and self-renewal. They have the potential to differentiate into different cell types or tissues. They are thought to form the roots of tumors,” Yang said.
Yang and his research team treated the mice with metformin before they developed tumors. After eight weeks, they were able to isolate tumor-initiating cells from the mice and determine that metformin substantially decreased the presence of the tumor-initiating cells.
“We found that the metformin resulted in a marked decrease in the tumor-imitating cells, specifically CD61high and CD49fhigh cells. This is different from all of the other studies because we used a spontaneous tumor model to demonstrate how metformin-induces prevention of HER2/neu breast cancer by targeting tumor-initiating cells or breast cancer stem cells. This will facilitate the development of novel strategies for breast cancer prevention,” Yang said.
On this study, Yang also collaborated with scientists at the NCA&T Center for Excellence in Post-Harvest Technologies and Rowan-Cabarrus Community College, both at the NCRC. His research was published in the paper “Metformin Selectively Targets Tumor-Initiating Cells in ErbB2-Overexpressing Breast Cancer Models” in the journal Cancer Prevention Research. He was invited for an oral presentation of his findings at the 2014 American Association for Cancer Research annual meeting.
With additional funding, he hopes to continue studying the mechanism by which metformin reduces tumor-initiating cells and help put a preventative option on the market that can improve the prognosis for women at risk of developing HER2/neu breast cancer.
Learn more about the NC Central University Nutrition Research Program.