Icahn School of Medicine at Mount Sinai
New York, New York
Chief of Breast Surgery, Mount Sinai Health System Director of the Dubin Breast Center, Mount Sinai Hospital Associate Attending, Tisch Cancer Institute Mount Sinai School of Medicine
Improving response to therapies in triple-negative breast cancer and identifying new targets for drug development.
Better therapeutic strategies are urgently needed for triple-negative breast cancer (TNBC), an aggressive form of breast cancer that is more likely to spread and is challenging to treat. Patient response to standard chemotherapy is highly varied, and few targeted therapies exist. Drs. Port, Irie and their teams are working to combat drug resistance in TNBC by developing a drug for the protein PRKCQ—a promising therapeutic target that, when inhibited, enhances sensitivity of TNBC cells to chemotherapy. This molecule sits at the nexus of several important processes in cancer cells that can drive drug resistance. PRKCQ may also have a role in the immune cells that infiltrate the tumor and targeting PRKCQ could potentially synergize with immunotherapies to drive an anti-cancer immune response.
Drs. Port and Irie’s teams successfully targeted PRKCQ in the laboratory with a novel drug that enhances sensitivity to chemotherapy in TNBC cells and suppresses their growth and ability to spread. Early results are promising but the drug is currently not suitable for human use. They also identified another signaling pathway that affects the same cellular processes as PRKCQ and developed a preliminary drug targeting this pathway, which also appears to reverse drug resistance in TNBC cells. More recently, the teams discovered that inhibiting PRKCQ reduces immunosuppressive activities in tumors, which would therefore enhance the activity of immunotherapies.
The team is collaborating with a small biotech firm to generate new versions of the PRKCQ drug that are more specific and will not affect any other proteins in the body, to minimize harmful off-target effects and toxicities. In the coming year, they will use these drugs in experiments to determine if blocking PRKCQ enhances the activity of a subset of immune cells known as cytotoxic T cells, which can directly kill tumor cells. They will also explore if their PRKCQ-blocking drugs synergize with checkpoint inhibitors, which are the most popular and efficacious immunotherapy available today.
Elisa Port, MD, FACS joined Mount Sinai Hospital and its Icahn School of Medicine in 2010. She serves as Chief of Breast Surgery and Director of the Dubin Breast Center. After receiving her medical degree from Mount Sinai in 1992, Dr. Port was a general surgery resident at Cedars-Sinai Medical Center in Los Angeles until 1994. She then joined Memorial Sloan Kettering Cancer Center for a breast cancer surgery research fellowship, and later completed a general surgery residency at Long Island Jewish Medical Center. In 1999, she joined the staff of Memorial Sloan Kettering Breast Surgery Service where she remained until her Mount Sinai appointment in early 2010.
Dr. Port performs hundreds of operations each year, and is a leading expert in sentinel-node biopsy, nipple sparing mastectomy, as well as the use of breast MRI.
Dr. Port is the author of “The New Generation Breast Cancer Book: How to navigate your diagnosis and treatment options-and remain optimistic- in the age of information overload”, recently published by Random House.
Dr. Port actively conducts both clinical and basic science research. With external grant support, Dr. Port researched PET scanning in the preoperative staging of patients with breast cancer, and also has conducted a trial investigating the role of COX-2 inhibitors in breast cancer. Her BCRF-supported research is focused on the development of new strategies to prevent triple-negative breast cancers from progressing and metastasizing.
Her research has been widely published in numerous journals, including the Journal of the American College of Surgeons, Annals of Surgery, and Cancer Research. She is also a member of several professional associations, including the American Society of Clinical Oncology, the American Society of Breast Diseases, the Society of Surgical Oncology, and is a Fellow of the American College of Surgeons.
2014
The Amy Robach Award
Icahn School of Medicine at Mount Sinai New York, New York
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