Memorial Sloan Kettering Cancer Center
New York, New York
Member, Department of Cell Biology and Genetics
Discovering new therapeutic targets to treat aggressive breast cancers.
Metastatic breast cancer (MBC), which is breast cancer that has spread to other sites in the body, is incurable and is the leading cause of breast cancer deaths. New treatment strategies are urgently needed that can prevent metastasis from occurring. Dr. Benezra has developed a novel targeted therapy called AGXA that has been shown to block tumor growth and metastasis in laboratory studies. His work could inform the development of a new class of well-tolerated, anti-metastatic drugs.
Dr. Benezra has made significant progress in identifying how AGXA works against a key target that is involved in the development and progression of breast cancer. He has discovered that AGXA kills breast cancer cells through the production of fat-containing molecules called lipids that are toxic to cancer cells but spare normal, healthy tissue. Dr. Benezra has made progress in identifying which lipid is responsible for killing cancer cells through the observed enhancement of killing when AGXA is combined with an FDA-approved diet drug that blocks the degradation and absorption of lipids. Finally, Dr. Benezra and his team have identified a protein in cancer stem cells that likely mediates a “resting” cell state, which shields it from standard chemotherapies and may refuel disease recurrence. These studies contribute to Dr. Benezra’s overarching goal of readying AGXA for clinical application and maximizing its chance for success in the treatment of breast cancer.
In the upcoming year, Dr. Benezra will learn more about the lipids that kill cancer cells in response to AGXA. These molecules will be synthesized and re-injected into cells or re-introduced using nanoparticle formulations.
Robert Benezra, PhD, is a Member at Memorial Sloan Kettering Cancer in the Department of Cell Biology and a Professor of Biology at Cornell Graduate School of Medical Sciences in New York City. As a postdoctoral fellow he identified the Id proteins as dominant negative regulators of the helix-loop-helix protein family and has since gone on to identify these proteins as key regulators of tumor growth, angiogenesis and metastasis. In addition, while at Sloan Kettering, Benezra and his colleagues identified the first human mitotic checkpoint gene, hsMad2, and demonstrated that its deregulation leads to chromosome instability, tumor progression and drug resistance. His program continues to focus on the molecular basis of tumor angiogenesis, tumor instability and metastasis. His current project supported by BCRF is to explore the therapeutic potential of a novel agent targeting the Id proteins for the treatment of aggressive triple negative breast cancers.
The Play for P.I.N.K. Award in Memory of Doris L. Mortman
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