Professor of Pharmacology and Medicine
Geisel School of Medicine
Hanover, New Hampshire
Women with a mutated breast cancer gene (BRCA) are at exceptionally high risk for developing breast cancer. Currently the only proven preventive strategy for these women is surgical removal of the breasts (bilateral prophylactic mastectomy). There is an urgent need to develop non-invasive, non-surgical alternatives. One such approach is chemoprevention, which is the use of drugs to prevent cancer formation. Drs. Liby and Sporn were the first to show that two drugs (olaparib and veliparib) are effective in delaying tumor formation in experimental models of BRCA1 breast cancer. These drugs belong to the class known as PARP inhibitors, which are currently in clinical trials for treatment of breast and ovarian cancer, but have not been previously investigated for prevention of breast cancer. The research team recently demonstrated that another type of drug called CDDO-Me could prevent BRCA breast cancers in experimental models. CDDO-Me is being tested in cancer patients for its ability to target immune cells and Drs. Liby and Sporn found that it can reprogram human immune cells so they can suppress the growth of breast cancer. In their ongoing studies they are testing new PARP inhibitors and new formulations for preventing breast cancer and evaluating other inhibitors that target the harmful effects of immune cells in breast cancer. Their long-term goal is to develop a safe and effective combination of chemopreventive drugs that would eliminate the need for prophylactic mastectomy. Such a chemopreventive regimen would be a great benefit to women with a BRCA mutation, who must presently suffer either the anxiety of “watchful waiting” or the disfigurement of radical surgery.
Michael B. Sporn received his MD degree at the University of Rochester, and then started a 35-year career at the National Institutes of Health, where he became the Chief of the Laboratory of Chemoprevention in the National Cancer Institute in 1978. In the 1980s his laboratory in Bethesda played a key role in the original discovery of the multifunctional cytokine known transforming growth factor-beta (TGF-beta). In 1995 he moved to Dartmouth, where he has held an endowed chair as Professor of Pharmacology and Medicine.
He has been a strong advocate for prevention of cancer for many years, and much of his own research has dealt with the development of new drugs to be used as chemopreventive agents. These drugs have included synthetic retinoids and rexinoids (analogs of vitamin A), synthetic deltanoids (analogs of vitamin D), as well as selective estrogen response modulators (SERMs). Most recently he has been focusing on the use of new synthetic triterpenoids as agents for preventing breast and lung cancer and for suppressing inflammation and oxidative stress.