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Mark I. Greene, MD, PhD, FRCP

University of Pennsylvania
Philadelphia, Pennsylvania

Titles and Affiliations

John Eckman Professor of Medical Science
Department of Pathology and Laboratory Medicine
Perelman School of Medicine

Research area

Developing new therapeutic approaches to prevent, treat, and eradicate breast cancer.


Several types of targeted treatments—drugs designed to specifically attack cancer cells while sparing healthy cells—have been approved for or are currently being studied for breast cancer. Unfortunately, drug resistance is a persistent challenge, particularly in advanced or aggressive tumors. Dr. Greene is working to improve outcomes for patients with advanced HER2-positive by identifying and engineering novel treatments for HER2-positive breast cancers that have metastasized or developed resistance to trastuzumab (Herceptin®), the standard HER2-targeted therapy.

Progress Thus Far

Dr. Greene has developed an inhibitor called ER121 that is highly effective against cancers with mutated EGFR, a gene involved in cell division and survival that is frequently dysregulated in HER2-positive and triple-negative breast cancers (TNBC). ER121 was shown to be effective against HER2-positive breast cancers in laboratory models, even those that are Herceptin-resistant. Dr. Greene previously showed in a breast cancer model that targeted therapy followed by administration of interferon, a molecule that activates immune cells, prevented breast cancer more effectively than therapy alone. Based on that result, Dr. Greene developed a highly effective drug delivery system, called ZED antibodies, that combines interferon with cancer drugs and significantly suppressed tumor formation in a breast cancer model.

What’s next

In the upcoming year, Dr. Greene will continue to test the effects of ER121 and ZED antibodies on Herceptin-resistant breast cancers and their utility in treating breast cancer-related brain metastases. He next plans to test it in a clinical setting. If successful, this novel drug will be established as a highly potent therapeutic for HER2-positive breast cancer, both in advanced and early-stage disease. Likewise, the ZED antibodies are expected to be tested in clinical studies soon.


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.

BCRF Investigator Since