Associate Professor of Pathology
Albert Einstein College of Medicine
Bronx, New York
Approximately 25% of breast cancers overexpress HER2, a protein found on the surface of tumor cells that is known to promote tumor growth. Targeted therapies against HER2-positive breast cancer, including traztuzumab and lapatinib, have been successful in stopping the growth of many, but not all of these tumors. Currently, there are no clinically validated markers of resistance to HER2 therapy. Dr. Hazan and her team recently discovered high levels of another growth-promoting protein called Fibroblast Growth Factor Receptor 4 (FGFR4) in HER2+ breast cancer cells and tumors. They believe that the two proteins might work together in driving an aggressive disease that is resistant to HER2-directed therapies such as trastuzumab. In her 2014-2015 BCRF study she will test whether neutralizing FGFR4 will re-sensitize tumors to HER2-based therapy in laboratory models of breast cancer to determine if combined therapy of FGFR4 and HER2 drugs might benefit those patients with advanced HER2+ breast cancer. Furthermore, the researchers believe that FGFR4 expression in HER2+ breast cancers might serve as a marker of resistance to targeted therapy and will work in collaboration with Dr. Joseph Sparano to evaluate whether this is the case.
Dr. Rachel Hazan received her PhD from George Washington University in 1990. She performed her thesis work under Dr. Joseph Schlessinger, where she studied Her2 signaling in breast cancer, and was the first to map Her2 phosphorylation sites. She then joined Dr. Gerald Edelman, a Nobel laureate at Rockefeller University and Scripps Research Institute to study adhesion molecules and their regulation in neuronal and epithelial cells. This served as a basis for her ongoing work on cadherin adhesion molecules and their role in breast cancer dissemination. In 1994, she joined MSKCC, where she initiated seminal studies on the role of cadherin switching in breast cancer progression. In 1997, she became Assistant Professor at the Mount-Sinai School of Medicine, and is presently Professor of Pathology at the Albert Einstein College of Medicine. Dr. Hazan has been studying the role of adhesion in invasion and epithelial to mesenchymal transition leading to metastasis. She showed that N-cadherin activates cancer spread by sustaining activation and signaling of the Fibroblast Growth Factor Receptor. Dr. Hazan discovered a variety of signaling pathways that contribute to metastasis and has so far elucidated key signaling modules including the MAPK, AKT and cell cycle regulators as critical promoters of metastasis. Her work uses laboratory models, cell culture systems and validation in clinical breast specimens. These models serve as a platform to elucidate mechanisms of metastatic spread with the goal of identifying pivotal targets for therapeutic application.