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Robert Benezra, PhD
Member, Department of Cell Biology and Genetics
Memorial Sloan Kettering Cancer Center
New York, New York
Goal: To discover new therapeutic targets to treat aggressive breast cancers.
Impact: Dr. Benezra’s work is focused on an agent called AGX51 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.
What’s next: He and his team will confirm the mechanism of action of AGX51 and investigate how cancer cells could potentially become resistant to its effects.
Metastatic breast cancer (MBC), which is cancer that has spread from the breast to other tissues in the body, is the leading cause of breast cancer deaths. Dr. Benezra is studying AGX51, an agent that reduces levels of certain proteins that have been identified as potential therapeutic targets to prevent metastasis. He is currently conducting studies that may advance this treatment to clinical trials.
Full Research Summary
Research area: Identifying new therapeutic agents that effectively inhibit the spread of breast cancer (metastasis).
Impact: 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. Thus, new treatment strategies are urgently needed that can prevent metastasis from occurring. Dr. Benezra is pursuing novel therapeutic targets for the treatment of MBC. He aims to apply his findings to the development of a new class of anti-metastatic drugs.
Current investigation: He and his colleagues are studying a class of proteins called inhibitor of DNA-binding proteins (ID proteins) as potential therapeutic targets to prevent metastasis. ID proteins are frequently overexpressed in breast cancer and have been implicated in breast cancer tumor growth and metastasis. Previous laboratory studies found that genetic knockdown of ID genes resulted in a reduction in tumor growth and lung metastases.
What he’s learned so far: Dr. Benezra has developed targeted anti-ID therapy, AGX51, which was shown to reduce lung metastases and cancer cell viability in laboratory studies.
What’s next: He and his team will continue their characterization of AGX51. They propose to study whether ID proteins are the primary targets of AGX51 and how cancer cells could potentially become resistant to the drug. They will also investigate the nature of ID-expressing cells and how they contribute to chemoresistance.
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 characterize and exploit a subset of patients' own white blood cells, called neutrophils, that act to inhibit early spread of breast cancer cells to distant organs.