Rachel Hazan, PhD
Bronx, New York
Professor of Pathology
Albert Einstein College of Medicine
Bronx, New York
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 largely unknown. Dr. Hazan seeks to uncover how cancer cells acquire the ability to spread to ultimately reveal 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. She has demonstrated that when GP2 activity is lost, it leads to excessive increase in blood vessel formation that enriches the cancer with oxygen and nutrients. This phenomenon is well-known—advanced breast tumors create their own vascular systems to facilitate metastasis, likely because of increased cancer cell entry into the blood. In the past year, Dr. Hazan discovered that GP2 loss causes most of the tumor to rely on glucose breakdown for energy supply, but that some tumor cells can survive under changing metabolic conditions, giving them a survival advantage that may lead to metastatic disease.
In the upcoming year, Dr. Hazan will continue her studies to understand how breast cancer spreads. Using state of the art technology called single-cell sequencing, she and her team hope to uncover novel drivers of metastasis that may give clues into remedies for metastatic breast cancer. Using this technology, Dr. Hazan has revealed that tumor cells lacking GP2 function also have increased levels of a factor that promotes epithelial to mesenchymal transition (EMT), a process by which normal epithelial cells gain migratory and invasive properties that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes and wound healing, but also in the initiation of metastasis. Dr. Hazan will determine whether GP2 loss regulates EMT. In addition, she and her team hope to uncover drivers of metastasis by identifying factors that induce EMT. These results could reveal potential targets that could be leveraged to prevent or treat 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.
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