Robert Benezra, PhD

Titles and Affiliations

Member, Department of Cell Biology and Genetics

Research area

Discovering new therapeutic targets to treat aggressive breast cancers.

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. New treatment strategies are urgently needed that can prevent metastasis from occurring. Dr. Benezra has developed a novel group of compounds called AGX that target and block ID proteins, which contribute to tumor growth and metastasis. His work could inform the development of a new class of well-tolerated, anti-metastatic drugs.

Progress Thus Far

Dr. Benezra has made significant progress in identifying how AGX drugs work against the development and progression of breast cancer. He has discovered that ID proteins produce reactive oxygen species (ROS) after they are targeted by AGX drugs and begin to degrade. These ROS oxidize fat molecules, which is highly toxic to cancer cells and kills them. Finally, Dr. Benezra discovered that breast cancer cells that express ID proteins and that are not actively proliferating can lay quiescent, making them resistant to standard chemotherapies. This chemoresistance may explain why breast cancer recurs and provides a rational basis for combining chemotherapy with AGX drugs to improve outcomes. These studies contribute to Dr. Benezra’s overarching goal of readying AGX for clinical application and opening up a new treatment option for patients with MBC.

What’s next

In the upcoming year, Dr. Benezra aims further understand the role of AXGA-induced ROS production on ID protein-targeted cell death. Finally, Dr. Benezra will continue to study the role of ID proteins in mediating the resting state responsible for chemotherapy resistance.

Biography

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.