Member, Department of Cell Biology and Genetics
Memorial Sloan Kettering Cancer Center
New York, New York
Breast cancer metastasis remains one of the greatest clinical challenges in breast cancer. Thus it is critical to identify new therapeutic agents that are effective in inhibiting the development of metastasis. Dr. Benezra’s laboratory is studying a class of proteins called DNA binding/differentiation (Id) proteins ( Id1 and Id3) as potential therapeutic targets to prevent metastasis. Id proteins have been shown to be overexpressed in primary and metastatic breast tumors and importantly, knocking out these proteins using genetic tools leads to a near complete inhibition of metastasis in experimental models. Dr. Benezra’s team identified an agent called AGX-51 that reduces the levels of Id1 and Id3 proteins leading to a decrease in lung metastases. When combined with the commonly used chemotherapy drug Taxol, AGX-51 further reduced lung metastases in a model of aggressive breast cancer. In the coming year, they will further investigate the antitumor activity of AGX-51 to better understand how it works to regulate Id1/Id3 proteins and will identify the gene expression changes associated with this action. These experiments are key to assessing the potential for novel anti-Id therapeutics in the management of metastatic breast cancer.
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.