Michael B. Sporn, MD

2009-2010 BCRF Project:
Co-investigator: Karen Liby, PhD, Dartmouth Medical School

There is a continuing need to devise new approaches to prevent breast cancer. This need is particularly compelling for the clinical management of women who have been newly diagnosed as carriers of BRCA mutations, and are therefore at exceptionally high risk for development of estrogen receptor (ER)-negative breast cancer. At present, there are no ideal choices for these women. Bilateral prophylactic mastectomy, which can reduce risk by 90%, is one option, but it is certainly not an acceptable one from a personal perspective. Chemoprevention that would be highly effective and acceptable for use for prevention of aggressive, ER-negative breast cancer in pre-menopausal women has yet to be developed.

Thus, the immediate goal of this project is to investigate promising new agents for preventing ER-negative breast cancer and to study their molecular and cellular mechanisms of action in this regard. The selection of new agents by Drs. Sporn and Liby at Dartmouth is based on drugs that are in advanced stages of pre-clinical development and therefore have the best possible chances for actual clinical implementation, if a high degree of efficacy and safety can be demonstrated in the studies they propose. Thus, the long-term goal of this project is to improve quality of life for women at exceptionally high risk for developing breast cancer by finding an effective and safe preventive drug regimen that would eliminate the need for bilateral prophylactic mastectomy. A similar strategy for chemoprevention of heart attacks and strokes in people at high risk, using cholesterol-lowering drugs (statins) and anti-platelet agents (aspirin), is widely accepted and effective.

Mid-Year Progress Report:
During the past six months Drs. Sporn and Liby have found that several new chemopreventive agents are effective drugs for suppressing the development of ER-negative breast cancer in experimental laboratory models. Hopefully their project will lead to the actual use of such drugs in women at high risk.

Bio:
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 1980's 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 Medical School, 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.