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Mark I. Greene, MD, PhD, FRCP
John Eckman Professor of Medical Science
Department of Pathology and Laboratory Medicine
Perelman School of Medicine
University of Pennsylvania
Goal: To develop new therapeutic approaches to prevent, treat, and eradicate breast cancer.
Impact: Dr. Greene has advanced the understanding of the role of HER2—a growth-promoting protein on the outside of breast cells—in breast cancer. He has also identified a new target for triple-negative (and possibly BRCA1) tumors that could lead to new treatment options.
What’s next: He and his team will conduct laboratory studies of therapeutic compounds that target HER2, EGFR (epidermal growth factor receptor), and a protein called survivin, which are important in tumor growth and progression.
Despite advances in targeted therapies, drug resistance remains a persistent challenge in the treatment of breast cancers, particularly in advanced or aggressive tumors. Dr. Greene is developing and testing novel therapies that have the potential to prevent drug resistance and improve breast cancer outcomes. His team has been focused on the development of targeted therapy to receptors such as HER2 and EGFR and the proteins they induce that contribute to the formation and progression of breast cancers.
Full Research Summary
Research area: Developing and testing novel therapies to improve outcomes in patients with breast cancer by preventing drug resistance.
Impact: Several types of targeted treatments for breast cancer, which are designed to specifically attack cancer cells while sparing healthy cells, have been approved for use or are currently being studied. Unfortunately, drug resistance is a persistent challenge in the treatment of breast cancer, particularly in advanced or aggressive tumors. Dr. Greene is identifying and engineering novel treatments to prevent resistance and improve outcomes for patients with advanced HER2 and triple negative breast cancers.
Current investigation: The team is focused on the development of targeted therapy to several receptors—including HER2 and EGFR—and the signals they regulate that contribute to the formation and progression of breast cancers. They’re also testing small therapeutic compounds that target HER2 proteins and a protein called survivin that is highly expressed in most cancers and is associated with a poor clinical outcome.
What he’s learned so far: Dr. Greene and his team identified a new class of molecules to inhibit survivin. They were also able to show that these inhibitors limited triple-negative breast cancer growth in laboratory models.
What’s next: The team will test the effectiveness of their compounds in the laboratory setting.
Mark I. Greene received his MD and PhD from the University of Manitoba in Canada, and the FRCP from the Royal College in 1976. In 1976 Dr. Greene moved from Canada to Harvard University. Professor Greene was appointed Assistant Professor at Harvard Medical School in 1978 and then Associate Professor in 1980. Greene was recruited to the University of Pennsylvania in 1986 as Professor of the Center of Receptor Biology. Dr. Greene was the Newton Abraham Professor of Medical Sciences, Oxford and is currently a trustee of the Abraham Research Trust Unit at the Dunn School and Oxford University.
Dr. Greene's laboratory developed an approach to target and down-modulate oncoproteins which, when expressed, were critical for abnormal growth. This simple approach developed in the neu system involved creating monoclonal antibodies specific for p185. He also developed the use of disabling receptor complexes with two antibodies specific for distinct regions of the receptor proteins. This approach is now approved (Herceptin and Perjeta). The development of a therapy that is useful in resistant tumors provides important insight into why resistance emerges in the first place.
Dr. Greene has developed new orally available classes of targeted therapeutics that will function to treat both early and far advanced breast cancer with fewer toxicities.