Two newly identified proteins that appear to play a critical role in the development of aggressive triple-negative breast cancer (TNBC) could also lead to potential new treatments, according to scientists at Icahn School of Medicine at Mount Sinai, the University of Kentucky, MD Anderson Cancer Center, and several medical centers in China.
Their findings, published in the February 10, 2014, issue of Cancer Cell, show how two key proteins activate the genes required for the rapid growth of TNBC cells. TNBC is particularly virulent, affecting roughly 15 percent of breast cancer patients; it spreads quickly and has a high likelihood of recurrence. Patients have limited treatment options.
“What we found is that triple-negative breast cancer is inflammation-associated cancer. Its rapid tumor growth and metastasis is heavily dependent upon specific gene-activation proteins,” says lead researcher Ming-Ming Zhou, PhD, of Mount Sinai. Dr. Zhou is the Dr. Harold and Golden Lamport Professor in Physiology and Biophysics, and serves as Chairman of the Department of Structural and Chemical Biology, and Co-Director of the Experimental Therapeutics Institute at Icahn School of Medicine at Mount Sinai.
The researchers found that by using a small-molecule compound they had designed to block the gene-activation mechanism in the two newly discovered proteins, they were able to stop the driving force behind the tumor growth in a mouse model of TNBC.
Dr. Zhou says a greater understanding of the cause of TNBC and development of a new targeted therapeutic agent based on this discovery could stop the disease from spreading or recurring. Through continued study, he hopes that human clinical trials of a new small-molecule compound could begin in another two to three years.
Triple-negative breast cancer derives its name from the lack of expression of three key cell-surface receptors: the estrogen receptor (ER), the progesterone receptor (PR), and human epidermal growth factor receptor (HER2/Neu). These cell-surface receptors allow hormones to bind to them, and are important in signaling between cells, as well as within cells.
The disease is primarily concentrated in women of African American and Hispanic descent, younger women, and women who have BRCA1 mutations.