Titles and Affiliations
Professor of Oncology and Medicine
Vincent T. Lombardi Comprehensive Cancer Center
Research area
Understanding how chronic stress affects breast cancer growth and treatment response, and whether blocking stress signals can improve outcomes.
Impact
Chronic stress has long been suspected to influence cancer outcomes, but the biological mechanisms behind this connection are not well understood. Dr. Lippman and his team have found that stress-related hormones, particularly norepinephrine, can make estrogen receptor (ER)-positive breast cancer cells more aggressive. When combined with estrogen, these stress signals increase tumor cell growth and resistance to standard anti-hormone therapies. Using laboratory models that model breast cancer, the team found that these aggressive traits can persist over time, suggesting that stress may essentially “reprogram” cancer cells into a more dangerous state.
Progress Thus Far
Dr. Lippman and his team discovered locking beta-adrenergic receptors, the target of common beta-blocker medications, did not reduce the cancer cells’ aggressive behavior. But blocking alpha-adrenergic receptors did significantly reduce it. This finding may help explain why beta-blockers have shown mixed results in past studies of women with ER-positive breast cancer, and points toward a more precise way to intervene. The team also identified a set of genes that become highly active in ER-positive breast cancer cells when exposed to both estrogen and norepinephrine together. This gene activity pattern is linked to substantially worse survival in women with Luminal A breast cancer, the most common subtype of ER-positive disease. Additionally, the team has begun to uncover the specific molecular pathways underlying how these stress hormones drive aggressive tumor behavior.
What’s next
In the coming year, Dr. Lippman and his team will further define the specific pathways driving aggressive tumor behavior under combined stress and estrogen signaling. They will test whether blocking these pathways can improve how well tumors respond to anti-hormone therapy in laboratory models. They will also investigate whether these stress-related gene patterns could be used to help predict outcomes for patients with breast cancer. Together, this research supports the team’s broader goal of developing new treatment strategies that combine stress reduction with standard therapies to improve outcomes for patients with breast cancer.
Biography
Marc Lippman, MD is a professor of Oncology and co-directs the breast cancer program at the Lombardi Comprehensive Cancer Center at Georgetown University. Prior to that he was the Kathleen and Stanley Glaser Professor of Medicine at the University of Miami Leonard School of Medicine and was Chairman of the Department of Medicine from May 2007 to May 2012 and Deputy Director of the Sylvester Comprehensive Cancer Center. Previously Dr. Lippman was the John G. Searle Professor and Chair of Internal Medicine at the University of Michigan. From 1988 through 1999 he was Professor of Medicine and Pharmacology and Chair, Department of Oncology, at Georgetown University in Washington, DC, and served as Director of the Lombardi Cancer Center. Dr. Lippman served as Head of the Medical Breast Cancer Section, Medicine Branch, at the NIH. He completed a Fellowship in Endocrinology at Yale Medical School from 1973-1974. He was Clinical Associate at the NCI from 1970-1971 and Clinical Associate at the Laboratory of Biochemistry of the NCI. From 1970-1988 he served as an Officer and Medical Director of the United States Public Health Service. Dr. Lippman completed his residency on the Osler Medical Service, Johns Hopkins University Hospital from 1968-1970. He has received numerous awards including Clinical Investigator Award, American Federation for Clinical Research in 1985; Transatlantic Medal and Lecture, British Endocrine Societies, 1989; the Astwood Award, Endocrine Society, 1991; the Bernard Fisher Award, University of Pittsburgh in 1991; the AACR Rosenthal Award in April 1994, and the Brinker Award for Basic Science of the Komen Foundation in 1994.
“If not for the BCRF, we would not have been able to develop the new models and innovative approaches that are crucial to the success of our high-risk high-reward work to explore RAGE as a vulnerability in breast cancer.”
