Professor of Pharmacology and Medicine
Geisel School of Medicine
Hanover, New Hampshire
Co-Investigator: Karen Liby, PhD, Geisel School of Medicine, Dartmouth College
Drs. Sporn and Liby have shown in the past year that the combination of two drugs is significantly more effective than either drug by itself in preventing breast cancer in a highly aggressive laboratory model. Both drugs have important effects in suppressing the tumor promoting actions of the inflammatory cells that drive the development of cancer. One of the drugs, SAHA, is already approved by the FDA for clinical use in treatment of cancer, and the other drug, CDDO methyl ester, has successfully completed phase I clinical trials for treatment of advanced cancer. For these new prevention studies, Drs. Sporn and Liby are attempting to use drugs that have potential for clinical application in women at high risk, with a goal of eliminating the need for bilateral prophylactic mastectomy.
For women with a mutated breast cancer gene (BRCA) who are at exceptionally high risk for developing breast cancer, it is important that alternatives to bilateral prophylactic mastectomy be developed. One such approach is chemoprevention, which is the use of drugs to prevent the original formation of cancers, rather than treating existing cancers. In their present studies, Drs. Sporn and Liby have just shown for the first time, that two drugs (olaparib and veliparib) are effective agents in laboratory models for delaying the formation of new breast cancers caused by BRCA mutation. These drugs belong to the class known as PARP inhibitors, which are currently in clinical trials for treatment of breast and ovarian cancer. PARP inhibitors have not been previously investigated for prevention of breast cancer, so the researchers believe that this new approach is worthy of further study, with the eventual goal of being able to use a PARP inhibitor for actual clinical use for prevention in women at exceptionally high risk.
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.