Penn Joins Major NCI Research Initiative to Advance
Breast Cancer Therapies
By applying new imaging technology and genetics, researchers will
tumor behavior and predict clinical outcomes
(Philadelphia, PA) – The University of Pennsylvania School
of Medicine was recently selected to become a member of the National
Cancer Institute’s Mouse Models of Human Cancers Consortium (MMHCC).
The MMHCC was established in 1999 to design and characterize mouse models
that more accurately reflect the way that human cancers develop and respond
to therapy. The research groups comprising the MMHCC at 24 lead sites
connect more than 50 institutions in the US and abroad and focus on mouse
models for cancers of major organ systems including prostate, breast,
lung, ovary, skin, colon, brain, and the blood and lymph systems.
Lewis A. Chodosh, MD, PhD, Vice Chair, Department of
Cancer Biology, Associate Investigator in the Abramson Family
Cancer Research Institute, and Program Leader of the Breast Cancer
Program at the Abramson Cancer Center, heads one of four
MMHCC sites at which breast-cancer models are being developed and studied.
Chodosh will oversee a $2.5 million, five-year program based at Penn that
encompasses multidisciplinary research from six institutions in three
countries. Chodosh’s co-principal investigators are: Mitchell
D. Schnall, MD, PhD, Associate Chair of Radiology at Penn; Robert
D. Cardiff, MD, PhD, of the University of California, Davis; and William
J. Muller, PhD, of McGill University.
The Penn Approach – A Focus on Breast Cancer
The goal of the Penn group is to develop new conceptual and technical
approaches for understanding the mechanisms of breast tumor progression
and metastasis. To accomplish this, Penn 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. “It’s truly a multidisciplinary team effort, bringing
together biologists with radiologists, nuclear chemists, physicists, pathologists,
and computational biologists,” says Chodosh. “This type of
endeavor requires a group of scientists with a tremendous breadth of knowledge
and expertise, which this grant has allowed us to assemble.
“Understanding cancer biology and response to therapy is so complex
a challenge that it requires changing the paradigm in which biomedical
research is performed,” explains Chodosh. “Traditionally,
biomedical research is performed by small groups of departmentally based
specialists working in relative isolation. In contrast, the MMHCC is based
on the premise that more rapid progress can be made towards curing cancer
by bringing together scientists from multiple, disparate academic disciplines
to work synergistically in an interdependent manner. Our group embodies
Specifically, the Penn MMHCC 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 distant metastasis
and recurrence. The technology will also be used to assess tumor response
to therapy and to predict clinical outcomes.
The mouse models for breast cancer to be used in this program are unique
in that the researchers can follow the entire natural history of the disease
in each animal – from initial onset to response to therapy, tumor
dormancy and, finally, metastasis and recurrence. “This process
may take two years in a given mouse, which is why using non-invasive imaging
approaches to follow the course of disease is so valuable,” explains
Chodosh. “Overall, we are bringing imaging, genetics, and cancer
biology to bear on these end-stages of breast cancer.”
Advanced stages of tumor progression, characterized by resistance to therapeutic
agents, metastasis, and tumor recurrence, are responsible for the majority
of cancer deaths. However, while tumor progression constitutes a problem
of unrivaled clinical importance, the underlying mechanisms are largely
unknown. Shedding light on the molecular and physiological events that
contribute to this process is a critical priority in cancer research.
“Genetically, we’re trying to identify the regulatory molecules
responsible for the ability of tumors to metastasize, recur, or remain
in a dormant state,” explains Chodosh. “Imaging permits us
to ask such questions as: Can we predict what a tumor will do in its natural
history? Will it metastasize? Will it recur? Will it respond to therapy?
Will this drug work or should we move on to the next drug?”
For example, using PET, researchers have already shown that patients with
a specific type of stomach cancer who respond to the drug Gleevec show
a dramatic change in glucose metabolism within 48 hours of taking the
drug. In this way, imaging has provided a vital and rapid indication about
response to therapy and survival that can be used to make decisions about
whether to change medication or not.
“With imaging you can look at metabolism, blood flow, and numerous
other physiological indicators important in tumor biology,” says
Chodosh. “And, due to the widespread clinical use of non-invasive
imaging, much of what we learn how to do in a mouse should be translatable
Additional key investigators in the Penn MMHCC group include Britton Chance,
PhD; David Tuveson, MD, PhD; Jerry Glickson, PhD; Paul Acton, PhD; Joel
Karp, PhD; Abass Alavi, MD; Chandra Sehgal, PhD; and Hank Kung, PhD, as
well as Ruth Muschel, PhD, at The Children’s Hospital of Philadelphia
and John Condeelis, PhD, at The Albert Einstein College of Medicine.
For more information on the MMHCC, go to http://emice.nci.nih.gov/emice/.
The Abramson Cancer Center of the University of Pennsylvania
was established in 1973 as a center of excellence in cancer research,
patient care, education and outreach. Today, the Abramson Cancer Center
ranks as one of the nation’s best in cancer care, according to U.S.
News & World Report, and is one of the top five in National Cancer
Institute (NCI) funding. It is one of only 39 NCI-designated comprehensive
cancer centers in the United States. Home to one of the largest clinical
and research programs in the world, the Abramson Cancer Center of the
University of Pennsylvania has 275 active cancer researchers and 250 Penn
physicians involved in cancer prevention, diagnosis and treatment.
PENN Medicine is a $2.7 billion enterprise dedicated
to the related missions of medical education, biomedical research, and
high-quality patient care. PENN Medicine consists of the University of
Pennsylvania School of Medicine (founded in 1765 as the nation’s
first medical school) and the University of Pennsylvania Health System
(created in 1993 as the nation’s first integrated academic health
Penn’s School of Medicine is ranked #3 in the nation for receipt
of NIH research funds; and ranked #4 in the nation in U.S. News &
World Report’s most recent ranking of top research-oriented medical
schools. Supporting 1,400 fulltime faculty and 700 students, the School
of Medicine is recognized worldwide for its superior education and training
of the next generation of physician-scientists and leaders of academic
Penn Health System is comprised of: its flagship hospital, the Hospital
of the University of Pennsylvania, consistently rated one of the nation’s
“Honor Roll” hospitals by U.S. News & World Report; Pennsylvania
Hospital, the nation's first hospital; Presbyterian Medical Center; a
faculty practice plan; a primary-care provider network; two multispecialty
satellite facilities; and home health care and hospice.