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Michael B. Sporn, MD
Emeritus Professor of Pharmacology and Medicine
Geisel School of Medicine
Hanover, New Hampshire
Goal: To identify safe and effective drug combinations for breast cancer prevention.
Impact: Individuals with mutations in one of the BRCA genes have a high risk of getting breast or other cancers. The only effective prevention strategy currently is prophylactic removal of the breast and ovaries. Drs. Liby and Sporn are seeking effective chemoprevention strategies as non-surgical prevention alternatives for women at high risk of breast cancer.
What’s next: Their current work is focused on immune cells that promote breast cancer cell growth and their role in triple negative breast cancer, the most common form of breast cancer in BRCA mutation carriers. They have identified a novel form of a rexinoid drug that blocks immune-cell activity. This year they will continue their efforts to identify drug combinations that can reduce the risk of breast cancer from high risk women or those affected by mutations in a BRCA gene.
Chemoprevention—the use of drugs to prevent cancer—has been shown to dramatically reduce the risk of certain types of breast cancers in women with a high risk of breast cancer or breast cancer recurrence. However, this is currently not an option for those with inherited mutations in the BRCA1 and BRCA2 genes. Drs. Liby and Sporn are testing several novel therapeutic strategies to suppress tumor-promoting immune cells and other growth processes to block tumor growth—work that could lead to alternative methods of cancer prevention in this high-risk group.
Full Research Summary
Research area: Identifying alternatives to prophylactic preventive surgery for women at high risk of breast cancer.
Impact: Women who carry inherited mutations in the BRCA1 or BRCA2 genes are more likely to develop breast cancer than women in the general population. Unfortunately, chemoprevention—the use of drugs to prevent cancer—isn’t an option for this high-risk group. The only proven preventive strategy for these women is to have their breasts surgically removed. Thus, there is an urgent need for less invasive, non-surgical alternatives.
Hoping to make chemoprevention available to women with BRCA mutations, Drs. Liby and Sporn are pursuing new drug combinations that would reduce the risk of breast cancer and reduce the need for surgical interventions.
Current investigation: The team has been testing the effectiveness of several drugs that could be used to prevent breast cancer in those with BRCA mutations. These include new formulations of PARP inhibitors, which are currently used to treat breast and other cancers caused by BRCA mutations, and new rexinoids (promising agents for chemoprevention).
What they’ve learned so far: Drs. Liby and Sporn have discovered that novel rexinoids favorably alter immune cells that drive tumor development. They have also shown that their new PARP inhibitors are more effective and less toxic than existing formulations and also favorably target the immune system. In addition, the team developed a high-throughput screen—a way of quickly testing large numbers of compounds—that they will use to identify agents that inhibit the transformation of normal cells into cancer cells.
What’s next: The team will continue synthesizing and testing new drugs and formulations that target immune cells known to promote the development and growth of breast cancer.
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.