September 20, 2012 — (BRONX, NY) — Why does cancer arise in certain parts of the body and not others? How exactly does it spread? These are critical questions that cannot be answered clearly despite decades of cancer research. Answers to complex but central questions about cancer have long stymied efforts to "win the war" on the disease.
Two research teams at Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center, the University Hospital for Einstein, have each been awarded grants from the National Cancer Institute (NCI) as part of their "Provocative Questions" program. The innovative effort is designed to ignite investigations into 24 promising but neglected or unexplored areas of research. Answering the questions would dramatically enhance ongoing efforts to prevent, treat and cure the disease.
Steven Libutti, M.D. (left), Richard Kitsis, M.D. (right)The Einstein-Montefiore grants – two of only 57 given nationwide and only five in New York City, and totaling more than $3 million over the next five years – are aimed at determining why cancer arises in certain tissues and how the disease spreads. Grant recipients are Steven Libutti, M.D., Richard Kitsis, M.D., John Condeelis, Ph.D., Sumanta Goswami, Ph.D., and Maja Oktay, M.D., Ph.D.
Both research teams will leverage the shared resources and unique assets of the two institutions to tackle their research projects, tapping into the clinical opportunities at Montefiore Einstein Center for Cancer Care and the advanced technical resources at the Albert Einstein Cancer Center and the Gruss Lipper Biophotonics Center.
The first grant, awarded to Drs. Libutti and Kitsis, will investigate why certain mutations promote cancer in some tissues of the body but not in others. The researchers will try to identify the factors responsible for this phenomenon, which they call "tissue-selective tumorigenesis."
The model they’ll be using in their study is a rare condition that results in human cancer called multiple endocrine neoplasia type 1 (MEN1). This inherited cancer results from a mutation in a gene called MEN1. Since MEN1 is a tumor suppressor gene, mutations in this gene permit tumors to occur. People with this cancer have a mutated MEN1 gene in every cell of their body, yet their tumors occur only in their endocrine glands (most often the parathyroid glands, the pancreas and the pituitary gland) and their duodenum (small intestine). The goal of this study is to discover why.
The researchers will take advantage of unique mouse models they developed and the fact that MEN1 tumors form only in the portion of the pancreas that produces insulin and other hormones and never in the "non-endocrine" part of the organ. Therefore, part of their research will involve comparing the two types of pancreatic tissue, looking for differences in gene expression.
John Condeelis, Ph.D. (left) Sumanta Goswami, Ph.D. (middle) Maja Oktay, M.D., Ph.D. (right)The second team of grant recipients, consisting of Drs. Condeelis, Goswami and Oktay, will focus on developing new approaches to investigating the biology of metastasis — the usually fatal spread of the primary cancer to other parts of the body. Using human breast cancer cells obtained from tumors of patients treated at Montefiore Einstein Center for Cancer Care, the scientists will focus on intravasation — the crucial step in which tumor cells invade blood vessels and are then carried to distant sites where they become seeded in new tissues.
The researchers have hypothesized that different breast tumors contain varying proportions of cells capable of invading blood vessels and that these "intravasation-competent" cancer cells have distinct gene expression profiles. The proportion of such tumor cells and the genes they express would determine whether a breast tumor metastasizes or not.
The goal of the research is to develop a human intravasation "signature" that will predict whether a breast cancer tumor is destined to metastasize. Identifying this signature will help to reveal targets for anti-metastatic therapies. Such therapies are urgently needed to decrease the morbidity and mortality associated with breast cancer.
Dr. Libutti is director of the Montefiore Einstein Center for Cancer Care, associate director of clinical services at Albert Einstein Cancer Center, professor of surgery and of genetics at Einstein, and vice chair of surgery at Einstein and Montefiore. Dr. Kitsis holds the Dr. Gerald and Myra Dorros Chair in Cardiovascular Disease and is professor of medicine and of cell biology and the director of the Wilf Family Cardiovascular Research Institute at Einstein. Dr. Condeelis is professor and co-chair of anatomy and structural biology, co-director of the Gruss Lipper Biophotonics Center, leader of the program in tumor microenvironment and metastasis in the Albert Einstein Cancer Center, and holder of the Judith and Burton P. Resnick Chair in Translational Research at Einstein. Dr. Goswami is assistant professor of anatomy and structural biology at Einstein and associate professor of biology at Yeshiva University. Dr. Oktay is associate professor of pathology (clinical) at Einstein and attending physician, pathology at Montefiore.
The MEN1 grant (CA170911) is for $1.7 million over 5 years; the metastasis grant (CA170507) totals $1.4 million over 4 years. The preliminary work for the MEN1 grant was funded by a generous gift from Linda and Earle Altman to Dr. Libutti. The preliminary data that made the metastasis grant possible were obtained from a gift from the Dempsey Family to the Albert Einstein Cancer Center that was awarded to Dr. Oktay in the fall of 2011.