$10 million awarded to study breast cancer progression using state-of-the-art imaging techniques and animal models to develop more effective therapies
(Philadelphia, PA) - The University of Pennsylvania School of Medicine has been named a Breast Cancer Center of Excellence by the Department of Defense Breast Cancer Research Program. This designation, which includes a five-year, $10 million grant to Lewis A. Chodosh, MD, PhD, Principal Investigator and Director of this Center of Excellence, establishes Penn as one of only 14 such sites in the United States. The Center represents a multidisciplinary approach to understanding breast cancer progression using genetically engineered mouse models and state-of-the art non-invasive imaging techniques.
"We are honored and proud to have earned this prestigious designation by the Department of Defense," says Dr. Arthur H. Rubenstein, Executive Vice President of the University of Pennsylvania for the Health System and Dean of the School of Medicine. "It is a testament to the high caliber of our physician-scientists and the programs they lead to have been selected to join the group of institutions named as Centers of Excellence. This award further strengthens our excellent research within the Abramson Cancer Center, which is dedicated to developing innovative and effective therapies for cancer patients."
The natural history of breast cancer involves the progression of cancer cells to adopt increasingly aggressive properties, such as resistance to chemotherapy and the ability to invade tissues and metastasize. What's more, by the time that breast cancers have been diagnosed, tumor cells may have already traveled to distant sites in the body where they may lay dormant in a clinically undetected state. Consequently, cancers that appear cured may resurface as local or distant recurrences 10 to 20 years later. Breast cancer progression – from disease onset to distant metastasis and recurrence – is ultimately responsible for essentially all breast cancer deaths.
"While tumor progression is a problem of unrivaled clinical importance, the mechanisms underlying it are poorly understood," says Chodosh, who is also Leader of the Breast Cancer Program at the Abramson Cancer Center, Director of Cancer Genetics at the Abramson Family Cancer Research Institute, and Vice Chair of the Department of Cancer Biology. "The biological and technical challenges to studying tumor progression and metastasis are considerable and explain why this area has been termed 'one of the last great frontiers of cancer biology.'" Because the process by which cancers progress and spread consists of numerous steps involving multiple organs, metastasis must be studied in whole animals. In addition, since the natural progression of breast cancers occurs over considerable periods of time, monitoring these events non-invasively facilitates their investigation.
To do this, Center researchers will employ a broad array of state-of-the-art cellular and molecular imaging techniques to analyze a series of novel, genetically engineered mouse models of breast cancer. Specifically, the group will use a comprehensive array of sophisticated technologies–including positron emission tomography (PET), magnetic resonance imaging (MRI), computed tomography (CT), magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT), and ultrasound–to visualize and follow tumor cells in living animals from their origins to their eventual progression to metastasis and recurrence. These animal models mimic key features of human breast cancer progression.
"Understanding the mechanisms that underlie breast-cancer progression will help us to understand the molecular basis for aggressive forms of this disease," says Chodosh. "Similarly, determining how and why breast cancer cells become dormant should lead to improved methods for finding and eradicating these cells, which are ultimately responsible for most breast-cancer deaths." By identifying the critical molecular targets and pathways by which breast cancers progress, the researchers hope to develop more effective therapies against highly aggressive forms of this cancer. In addition, non-invasive imaging will likely aid in the identification of aggressive tumors, as well as early signs of tumor response to therapy.
Penn researcher Mitchell Schnall, MD, PhD, Vice Chair of Radiology at Penn, and Ruth Muschel, MD, PhD, former Abramson Cancer Center member, are co-Principal Investigators of the grant. The Center, which is based at Penn, includes two dozen investigators at Penn, the University of California Davis, Albert Einstein College of Medicine, McGill University, and the Children's Hospital of Philadelphia.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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