Marc E. Lippman, MD
Kathleen & Stanley Glaser Professor
Chairman, Department of Medicine
Miller School of Medicine, University of Miami
2013-2014 BCRF Project:
(The Bloomingdale's Award)
Dr. Lippman’s overall goal is to determine the relationship between tumor cytokine production, myeloid cell recruitment to primary tumors and their role in breast cancer metastasis. In 2012-2013, Dr. Lippman’s team has made considerable progress in characterizing immune cells recruited by different subtypes of primary breast tumors in laboratory models. They have additionally confirmed that, in at least five metastatic breast cancer models, tissues bearing cancer cells—whether it is the primary site or a metastatic lesion—exhibit changes in gene expression that are consistent with an infiltration of myeloid cells and is common throughout their models. This characterization of intratumoral immune cells—or immunophenotyping—together with the shared gene expression changes, and the tumor-derived factors Dr. Lippman’s team has quantified in these models has given them important information on the relationship between cancer cells, their local and systemic environment and revealed potential novel targets as therapeutic alternatives. Dr. Lippman has initiated a laboratory model trial protocol aimed at disrupting the modulation of the immune system by the cancer cells. To do this, the researchers treat these models of breast cancer with an agent that in other types of cancer has been shown to have an anti-angiogenic effect and modulate the immune system to be more anti-tumor. Their preliminary data suggest this agent may have similar properties in at least one model of breast cancer. Additionally, they have focused on surveying the presence of such factors circulating in plasma samples of breast cancer patients, which had been previously shown to have an increased number of myeloid derived suppressor cells (MDSCs) in circulation. The former correlates with a poor prognosis. Their data show that compared to healthy individuals, plasma of advanced stage breast cancer patients exhibited higher levels of at least six different factors. These results may shed light on the critical immune-modulatory signaling that leads to and favors the development of metastatic disease.
Dr. Lippman’s aim for the coming year is to provide strong pre-clinical data derived from a comprehensive analysis of the effect of the novel therapeutics they are –and will be-- testing in more than seven different models of metastatic breast cancer, including immunosuppressed as well as models that have a fully functional immune system, that may ultimately be taken into the clinic as a novel therapy for metastatic breast cancer. In the upcoming year, he and his team will conduct a clinical pilot study to expand their preliminary observations of increased cytokine levels in plasma of advanced stage breast cancer patients. Thus, understanding biological events that predispose a patient to, and favor the development of, metastatic disease is of monumental importance, as this is the main cause of mortality of breast cancer patients. This work has the potential to provide a significant gain of knowledge on the interaction between the host and the cancer cells, and how modulation of cytokine “balance” needs to be taken into consideration in breast cancer research."
Dr. Lippman’s current research is focused in identifying and pursuing tumor induced changes in host immune competency as a critical factor driving the metastatic process. To this end, he and his colleagues have used several models of human breast cancer—both metastatic and non-metastatic, in which they have quantified circulating cytokines and the number of immune cells and proportion of the myeloid subtypes infiltrating the different tumors. Their previous studies have shown that the presence of these myeloid cells favors tumor growth and progression. Because the tumor-secreted factors are responsible for the arrival of these cells to the primary tumor, the researchers believe it is critical to identify such factors and interrupt the communication between metastasis-prone primary tumors and recruitment of myeloid cells by decreasing their effectiveness or numbers. Encouraging preliminary data with experimental models of breast cancer suggest that 1) individual tumors secrete a unique combination of cytokines; and 2) models with metastatic disease have increased levels of inflammatory cytokines contributed by tumor [human] and stromal [model] cells. Similar preliminary data is observed from their results in a pilot study comparing levels of inflammatory markers in stage IV breast cancer patients to healthy individuals. To further expand these observations, the researchers are currently conducting a clinical study to quantify inflammatory cytokines and myeloid derived suppressor cells (MDSCs) in two groups of breast cancer patients: cured DCIS and stage IV breast cancer. In these samples, the detected inflammatory cytokines are the summation of those derived from breast cancer cells and non-cancer cells (immune cells or cells from the tumor microenvironment).
Importantly, recent data have shown that central obesity and depression are diseases that tend to be associated with high levels of inflammation, and are associated with higher incidence of cancer and higher rates of recurrence. Furthermore, Dr. Lippman’s work has the potential to show that the same means by which breast cancer cells alter the host environment in a pro-metastatic way, pre- or co-existing inflammatory states can encourage breast cancer progression through common mechanisms. These studies will lead to information which will directly improve the outlook for women with breast cancer and may with a particular beneficial impact on women with co-morbidities including depression and obesity.
Dr. Marc E. Lippman, MACP, was named the Kathleen and Stanley Glaser Professor of Medicine at the University of Miami Leonard M. Miller School of Medicine, and was named Chairman of the Department of Medicine in May 2007. Previously Dr. Lippman was the John G. Searle Professor and Chair of Internal Medicine at the University of Michigan, Ann Arbor, Michigan. From 1988-1999, Dr. Lippman was Professor of Medicine and Pharmacology and Chair of the Department of Oncology at Georgetown University in Washington, DC. He also served as Director of the Lombardi Cancer Center at Georgetown University Medical Center. From 1978-1990 he was Clinical Professor of Medicine and Pharmacology, Uniformed Services, University of the Health Sciences. Dr. Lippman served as Head of the Medical Breast Cancer Section, Medicine Branch at the National Institute of Health. He was a Senior Investigator at the National Cancer Institute of the National Institute of Health.
Dr. Lippman completed a Fellowship in Endocrinology at Yale Medical School in New Haven, CT from 1973-1974. In addition, he was Clinical Associate at the National Cancer Institute from 1970-1971 and Clinical Associate at the Laboratory of Biochemistry of the National Cancer Institute of the National Institute of Health. From 1970 to 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 at John Hopkins Hospital in Baltimore, Maryland from 1968-1970.
A native of New York, Dr. Lippman received his bachelor’s degree from Cornell University, Magna Cum Laude, and medical school degree from Yale Medical School in New Haven, CT where he was elected to the Alpha Omega Alpha (AOA) Honor Medical Society.
Dr. Lippman is widely known for his research in breast cancer. Throughout his illustrious career he has received numerous awards. He also has been the first recipient of the William P. McGuire Memorial Lecture, San Antonio, TX in 1992, and the Howard University Outstanding Achievement Award in 1993. He also received the First American Cancer Society Lectureship and Prize at the American Society of Clinical Oncology (ASCO) Meeting in Orland, FL in May 1993, the American Association for Cancer Research (AACR) Rosenthal Award in April 1994, and the Brinker Award for Basic Science of the Komen Foundation in 1994. Dr. Lippman also owns several patents including Ligand Growth Factors that bind to the ERBB-2 Receptor protein and induce cellular responses.
Dr. Lippman is a member of the Association of American Physicians, the American Society for Clinical Investigation, the American Society of Biological Chemists, AACR, and ASCO. He has recently received the honor of Masters of the American College of Physician. As a researcher, Dr. Lippman has published over 400 peer reviewed articles. In addition, he has authored many books and contributed many chapters based on his breast cancer research including a textbook on breast disease.
Dr. Lippman has served on the Editorial Board of numerous publications including Breast Cancer Research and Treatment, for which he serves as Editor-in-Chief, the Journal of Steroid Biochemistry, The Cancer Journal, Cancer Research, Breast Disease, Cancer Therapeutics, the LOWAD Journal Women and Cancer, Signal, and the American Journal of Oncology Review. In addition, he has been Editor-in-Chief of Endocrine-Related Cancer.