Five-year breast cancer survival rates have improved dramatically over the past 50 years, but tumors can recur up to ten or more years after they are detected. When tumors recur, they are even more difficult to treat. Recurring breast tumors often don't respond to targeted drugs, even if the initial tumor did, and they metastasize-spread to other parts of the body-more easily. To help women battling breast cancer, Eric Prossnitz, PhD, is investigating GPER, a new type of estrogen receptor, as a possible new drug target. Unlike "classical" estrogen receptors ER-a and ER-b, GPER resides on cell membranes rather than in the cell's nucleus. Dr. Prossnitz is a University of New Mexico Professor of Cell Biology & Physiology and Co-Leader of the Women's Cancers Program at the UNM Cancer Center. He recently received a 5-year, $1.6 million grant from the National Cancer Institute to study GPER, its role in resistance to drugs that target estrogen receptors, and possible new ways to target it in combating breast cancer.
Like other cell membrane receptors, GPER tells the cell what's happening around it. Much like humans see and hear their surroundings, each cell has different types of receptors to sense its environment. For example, breast cells have multiple receptors, including hormone receptors that sense estrogen and progesterone and a group of receptors that senses growth factors, which includes the HER2 receptor. Most breast cancer drugs target one or more of these receptors. Women whose breast cancer cells lack all three receptors, called triple negative breast cancers, must resort to surgery, chemotherapy and radiation. Dr. Prossnitz discovered in previous research that Tamoxifen, a breast cancer drug that works by inhibiting ER-a receptors, activates GPER. Now Dr. Prossnitz wants to determine whether and how GPER influences breast tumor growth and metastasis.
Dr. Prossnitz is collaborating with Helen Hathaway, PhD, UNM Professor of Cell Biology & Physiology and a member of the Women's Cancers Program, to conduct studies on GPER. In the first study, Drs. Prossnitz and Hathaway will use cancerous and non-cancerous breast cells to discover the differences in biochemical reactions that estrogen receptors and GPER trigger. Both receptors ultimately stimulate enzymes that regulate cell growth and survival, but researchers know little about how the cascades of cellular reactions differ. Understanding this biochemistry will help Drs. Prossnitz and Hathaway explain how breast cancer cells respond to estrogen and become resistant to Tamoxifen, potentially resulting in better long-term breast cancer therapies.