Robert Benezra, PhD
Member, Department of Cell Biology and Biology
Memorial Sloan-Kettering Cancer Center
New York, New York
2012-2013 BCRF Project:
(made possible by generous support from Play for P.I.N.K.)
Dr. Benezra's preliminary laboratory results showed that neutrophils (a component of the immune system), stimulated by the primary tumor, have anti-metastatic properties and have the capacity to kill tumor cells. Their new data show that tumor entrained neutrophils (TENs) are generated in newly diagnosed patients with both invasive and localized breast tumors, but not in healthy volunteers or in patients who had their tumors surgically removed. Furthermore, Dr. Benezra's team showed that the tumor-cell killing activity in neutrophils could be induced. These studies suggest a plausible strategy for periodically delivering a patient's own neutrophils in order to inhibit metastatic progression in high-risk patients post-surgery and may provide an additional method to prevent the recurrence and spread of breast cancer.
In 2012-2013, Dr. Benezra's team will assess neutrophil cytotoxicity in a larger cohort of patients with invasive tumors arising from either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) (50 patients per group). Neutrophils from these patients will be analyzed prior to tumor removal/chemotherapy and in the months following surgery and chemotherapy. In addition, Dr. Benezra and his colleagues will try to correlate patient parameters, such as hormone receptor status and the circulating levels of specific chemokines, with neutrophil cytotoxicity in breast cancer patients with invasive tumors. In addition, they will assess the feasibility of a neutrophil mediated anti-metastatic therapy. To this end, the Benezra team will optimize a protocol for efficient collection and in vitro entrainment of neutrophils. They will then test the efficacy of supplementing conventional chemotherapies with entrained neutrophil transfusion in laboratory models of metastatic breast cancer.
Mid-year Progress: Metastasis, or the spread of breast cancer cells beyond the mammary gland, is a major clinical problem that needs to be addressed with a better understanding of the process and new strategies to inhibit it. Dr. Benezra's team has identified a type of cell in the immune system that has the capacity to inhibit the growth of breast tumor cells in the lung and has learned what types of factors entrain these cells to acquire this property. Patients with higher levels of these cells may be at reduced risk for metastasis. By treating these immune system cells isolated from a patient, the investigators have identified that this treatment makes them better cancer cell killers and they hope to be able to return these cells to the patient and thereby reduce the likelihood of breast cancer spread with little toxicity.
Robert Benezra, PhD, is a Member at Memorial Sloan-Kettering Cancer (MSKCC) in the Department of Cell Biology and a Professor of Biology at Cornell Graduate School of Medical Sciences in New York City. Before he joined MSKCC, Benezra worked at Fred Hutchinson Cancer Center in Seattle where 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 MSKCC, Benezra and his colleagues identified the first human mitotic checkpoint gene, hsMad2, and demonstrated that its de-regulation 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 and is currently developing molecular and cellular tools to inhibit these processes in patients.