Rachel Hazan, PhD
Associate Professor of Pathology
Albert Einstein College of Medicine
Bronx, New York
2013-2014 BCRF Project:
(The First Step Award, made possible by QVC and Fashion Footwear Charitable Foundation)
Co-Investigator: Larry Norton, MD, Memorial Sloan-Kettering Cancer Center, New York, NY
Drs. Hazan and Norton’s project focuses on the N-cadherin molecule, which is often found to be hyperactive in aggressive breast cancers. N-cadherin in breast cancers, driven by the HER2/neu oncogene, causes tumor cells to become more metastatic. Drs. Hazan and Norton observed in the laboratory that this molecule stimulates the spread of cancer cells -- a finding that implies the targeting of N-cadherin might prevent the spread of tumor cells, and new therapies could be developed. Since relatively little is known about N-cadherin and its functions, this team set out to delineate the exact mechanisms of N-cadherin action on breast cancer metastasis. Their ultimate aim is to turn that information into new clinical strategies for metastasis prevention.
Dr. Hazan has found in a survey of 99 invasive breast cancers that N-cadherin was co-expressed with HER2/neu in poorly differentiated tumors. This combination of HER2 and N-cadherin caused the breast tumor cells to behave like cancer stem cells. These stem cells were readily eradicated by FGFR or MEK inhibitors. They recently recently found that the switch from the benign E-cadherin molecule to the malignant N-cadherin is facilitated by a molecule called Akt3. Therefore understanding how Akt 3 is regulated in breast cancer will allow understanding of how to reverse the adhesion molecule switch in favor of an anti‐cancer state. In 2013-2014, Drs. Hazan and Norton will further investigate these findings to decipher the role of N-cadherin in breast cancer.
During the past several months, Drs. Hazan and Norton found that Akt3 expression is lost with progression from a normal/benign to a malignant breast cancer form, suggesting activating the expression of Akt3 in cancer can combat cancer formation. Their team is now testing this hypothesis in laboratory models using human cancer transplants.
Dr. Rachel Hazan received her PhD from George Washington University in 1990. She accomplished her thesis work in the laboratory of Dr. Joseph Schlessinger where she studied the role of Her2/neu signal transduction in breast cancer. During this work, she characterized the tyrosine phosphorylation sites on Her2/neu and generated a panel of monoclonal antibodies against HER2/neu which were successful in suppressing breast cancer cell growth and transformation.
She then joined the laboratory of Dr. Gerald Edelman at Rockfeller University and Scripps Research Institute as a postdoctoral fellow to learn about adhesion molecules which were just beginning to be implicated in cancer progression. This background served as a basis for her current work in which she is investigating how cadherin adhesion molecules and growth factor receptors cooperate in tumor metastasis.
In 1994, she joined the department of Surgery at Memorial Sloan-Kettering Cancer Center as an Assistant Laboratory Member and initiated work on the role of adhesion molecules in breast cancer. In 1997, she joined Mount-Sinai School of Medicine as an Assistant Professor and in 2003 the Albert Einstein College of Medicine as Associate Professor of Pathology.
Dr. Hazan found that a neural cadherin, N-cadherin was overexpressed in most invasive and metastatic human breast cancer cell lines and tumors. N-cadherin induces metastasis due to its ability to bind and potentiate signaling by the FGF receptor. She is currently pursuing the genes and downstream signaling pathways that are promoted by the N-cadherin-FGFR axis as well as how N-cadherin adhesive interactions with the host microenvironment also play a role in tumor dissemination. Her current studies involve the use of transgenic breast cancer mouse models in which mammary co-expression of N-cadherin with the PyVmT antigen or the Her2/neu oncogene were found to dramatically increase the metastatic potential of breast cancer cells. These models will serve as a basis to determine the molecular mechanisms underlying N-cadherin metastatic activity and identify targets for translational or therapeutic application in breast cancer.