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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 or are currently being studied for breast cancer. Unfortunately, despite a targeted approach, 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 breast cancer by identifying and engineering novel treatments for HER2-positive breast cancers that have metastasized or developed resistance to trastuzumab (Herceptin®), a 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). Dr. Greene has shown that ER121 not only appears to be effective against HER2-positive breast cancers in laboratory models, but more effective than currently available HER2 therapies. His team found that ER121 is effective even in Herceptin-resistant breast cancers and arrests tumor growth.

What’s next

In the upcoming year, Dr. Greene will focus on developing oral ER121 to prevent the development of HER2-positive breast cancer. So far, the team has early data showing that ER121 is active orally and can prevent and treat brain metastases when given intravenously. If successful, Dr. Greene aims to test this promising HER2-positive breast cancer therapy in clinical trials.


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