Hanna Irie, MD, PhD
New York, New York
Associate Professor of Medicine and Oncological Sciences
Icahn School of Medicine at Mount Sinai
New York, New York
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. Irie and Port, 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. Irie and Port’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.
The team is collaborating with a small biotech firm to generate new versions of the PRKCQ drug that are more specific and won’t affect any other proteins in the body, to minimize harmful off-target effects and toxicities. They will then continue their laboratory studies to validate the effectiveness of both of their resistance-targeting drugs. In addition, they will confirm the relative abundance of PRKCQ and their alternative signaling pathway in samples taken from chemotherapy-resistant TNBC tumors, to confirm these processes occur in patients. And finally, the team will also explore the effect of their drugs on the immune cells within TNBC tumors, to see if they can enhance the effectiveness of immunotherapies, which currently have very limited use in TNBC.
Dr. Irie is Assistant Professor of Medicine and Oncological Sciences at the Tisch Cancer Institute and Dubin Breast Center of Icahn School of Medicine at Mount Sinai in New York City. She received her MD and PhD degrees from Harvard Medical School and completed a residency in Internal Medicine at Massachusetts General Hospital, followed by a clinical fellowship in Hematology and Medical Oncology at the Dana-Farber Cancer Institute. As a medical oncologist, she specializes in the treatment of patients with breast cancer, with a special focus on improving care for patients with triple negative cancers for whom current treatment options are limited. In addition to patient care, she directs a lab-based translational breast cancer research program. The challenges faced by many of her patients drive the focus of the program's research. Her laboratory focuses on identifying novel therapeutic targets for breast cancer, particularly for treatment-resistant breast cancers, and understanding the mechanisms by which these candidate genes regulate breast tumor cell behavior. They are also developing models that more accurately mirror treatment-resistant triple negative cancers so that they can be used to validate more effective treatment strategies and support clinical studies.
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