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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
Philadelphia, Pennsylvania

Current Research

  • Seeking to develop new therapeutic approaches to prevent, treat, and eradicate breast cancer.

  • Efforts are ongoing on the development and validation of several novel potential therapies to improve outcomes for patients with advanced HER2 and triple negative breast cancers. 

  • Dr. Greene's group is actively developing and testing novel therapies that have the potential to prevent drug resistance and improve breast cancer outcomes.

In spite of advances in targeted therapies, drug resistance is a persistent challenge in the treatment of breast cancers, particularly in advanced or aggressive tumors. Dr. Greene is conducting studies to identify new treatment strategies designed to prevent drug resistance. Some of these work by turning on the anti-tumor immune response, others by blocking key pathways regulating cell growth. 

Full Research Summary

Dr. Greene's group is actively developing and testing novel therapies to improve patient outcomes by preventing drug resistance. Using methods developed in his laboratory, Dr. Greene's team works to synthetically engineer novel drugs that target the family of ErbB proteins, of which HER2 is a member. 

Ongoing studies have identified new potential drugs with low toxicity that block tumor growth in laboratory models of HER2-positive and triple negative breast cancers. Dr. Greene’s group is currently testing this new therapy in combination with molecules that activate the immune system to enhance the anti-tumor effect. In addition, they have engineered a novel Herceptin®-like antibody that is designed to be more effective than Herceptin® at treating advanced HER2 tumors that have become resistant to targeted therapy. 

This year, the team is developing new treatments for triple negative breast cancers that overexpress a potent growth factor called EGFR and tumors caused by mutations in the BRCA genes. They are testing a therapy that blocks a protein called Survivin that is involved in cell division and have identified specific inhibitors of the Survivin protein. This study has exciting potential to improve treatment in aggressive tumors.


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.

Grid Researcher Headshot - Greene M

BCRF Investigator Since


Area(s) of Focus