Titles and Affiliations
Associate Professor of Medicine and Oncological Sciences
Research area
Developing new treatments for drug-resistant hormone receptor-positive breast cancer.
Impact
Most breast cancers are hormone receptor (HR)-positive, and while many patients respond well to standard treatments, some cancers become resistant to therapies and continue to grow and spread. Understanding why resistance develops and finding new ways to overcome it are major areas of research, since resistant HR-positive breast cancers are harder to treat and often require more aggressive therapies.
Progress Thus Far
Drs. Irie and Port are developing two approaches to address drug-resistant HR-positive breast cancer. First, they identified a gene called PTK6 as an important driver of resistance to anti-estrogen therapy. They have developed first-in-class “degrader” drugs that reduce PTK6 levels in cancer cells, causing them to die. These degraders have shown strong anti-tumor activity in laboratory models. Second, a gene called MYC drives resistance to both anti-estrogen therapy and CDK4/6 inhibitors in a subset of HR-positive breast cancers. The team developed a new compound that targets a unique vulnerability tied to how MYC-expressing cancer cells generate energy and survive. This compound effectively kills HR-positive cancer cells that have become resistant to standard treatments.
What’s next
The team will test both the PTK6 degraders and the MYC-targeting compound using laboratory models developed from patient tumors. These studies will help them better understand how the treatments work and assess how well they stop tumor growth in drug-resistant cancers. They will also optimize the PTK6-targeting degraders for future clinical trials and further investigate how the compound’s target contributes to cancer cell survival. If successful, this work will lay the foundation for new treatment options for patients with metastatic, drug-resistant HR-positive breast cancer.
Biography
Hanna Irie, MD, PhD is Associate Professor of Medicine in the Division of Hematology and Medical Oncology and in the Department of Oncological Sciences at the 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. The focus of her research is to identify and validate novel therapeutic strategies for high risk and metastatic breast cancer. Recent research efforts have focused on oncogenes that regulate ephithelial-mesenchymal transition, drug resistance and metastases of breast cancer cells. Her laboratory collaborates with chemical biologists to develop and validate novel therapeutics targeting oncogenes and pathways. She and Dr. Port have worked on the generation of novel patient-derived estrogen receptor (ER)-positive and triple negative breast cancer (TNBC) models that enable validation of novel therapeutics. Their work further investigates biomarkers of chemotherapy and immunotherapy resistance to complement validation of these novel therapeutics. She and Dr. Port serve as co-PIs of the Mount Sinai Breast Tumor Biospecimen Repository which has banked over 500 breast tumor specimens.
“If not for BCRF, we would not have been able to take on the challenges associated with developing novel therapeutics for triple-negative breast cancer, from identification of new gene targets to drug design and validation.”
