Robert Benezra, PhD

2011-2012 BCRF Project:
(made possible by generous support from Play for P.I.N.K.)

Dr. Benezra's preliminary results showed that neutrophils (a class of white blood cells) accumulate in the lungs of laboratory models of breast tumors prior to metastasis (the spread of the tumor). He and his laboratory team further showed that these tumor entrained neutrophils, 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 also generated in patients with invasive mammary tumors and that several factors that emanate from the tumor and can induce tumor-cell killing activity in human neutrophils.

In 2011-2012, Dr. Benezra and colleagues will assess neutrophil cytotoxicity in a larger cohort of patients with invasive tumors, both ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS), with 50 patients in each group. Neutrophils from these patients will be analyzed prior to tumor removal/chemotherapy and in the months following surgery and chemotherapy. In addition, these researchers will try to correlate the hormone receptor status and the circulating levels of specific chemokines with neutrophil cytotoxicity in breast cancer patients with invasive tumors. These studies led by Dr. Benezra aim to bring us closer to safe and effective cell based therapy in the management of breast cancer metastasis.

Mid-year Progress: Dr. Benezra's team has found that many breast cancer patients with invasive primary tumors have neutrophils in their circulation that are capable of killing cancer cells before they have a chance to metastasize to the lung. These neutrophils are entrained to kill by chemicals which the investigators have identified that are secreted by the primary tumor in the breast. Dr. Benezra and colleagues have also shown that, once a primary breast tumor is removed by the surgeon, the killing capacity of these neutrophils is reduced because the entraining chemicals are no longer present and this may increase the risk of metastasis to the lung. This risk the researchers believe can be reduced by re-introducing normal neutrophils that have been exposed to these chemicals outside the body. Certain breast cancer patient populations, e.g. African American women, seem to be at higher risk as their neutrophils have significantly lower killing capacity even prior to surgery. This team's most recent experiments demonstrated that even short exposures of neutrophils to these chemicals outside the body is sufficient to allow these neutrophils to acquire potent anti-cancer killing capacity. This type of cell-based therapy after surgery may become a non-toxic way of reducing the risk of breast cancer metastasis, the major cause of mortality.

Bio:
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.