Albert Einstein College of Medicine
Bronx, New York
Professor of Pathology
Understanding what drives tumor growth and survival in order to prevent the spread of breast cancer.
Metastasis—the spread of tumors to other tissues—is the main cause of death from breast cancer. While treatable, metastatic breast cancer is currently incurable. Metastasis is a complex, multi-step process. For tumors to metastasize, cancer cells must travel through the bloodstream or lymphatic system. The mechanisms that give cancer cells the ability to travel through the body and colonize new sites, however, are still emerging. Dr. Hazan seeks to uncover how cancer cells acquire the ability to spread to develop new therapeutic strategies to prevent metastasis from occurring.
Dr. Hazan has shown that an enzyme called glutathione peroxidase 2 (GP2) is a strong inhibitor of metastasis. The loss of GP2 activity in breast cancer has been shown to be associated with short-term survival of breast cancer patients. Dr. Hazan discovered that loss of GP2 function in breast cancer cells renders them highly metastatic and seeks to understand exactly how turning off the GP2 gene contributes to metastasis. She and her team identified a subset of cells in both the primary tumor and the metastasis that drive aggressive behavior through activation of specific genes. This is important because they are now able to pinpoint subpopulations of cancer cells within the primary tumor that are active in the process of metastasis.
In the upcoming year, Dr. Hazan investigate the genes that promote metastatic behavior and uncover how they work. She will also test a drug that is known to inhibit activation of one of the identified genes in the hopes that it will suppress metastasis. Next, Dr. Hazan will try suppressing other identified genes using molecular biology techniques and observing the characteristics of tumor cells to further distinguish what drives metastasis.
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 Memorial Sloan Kettering Cancer Center, 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.
The Neil and Jane Golub Award
Memorial Sloan Kettering Cancer Center
New York, New York
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