Washington, DC Scientists at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC) were awarded a five-year $7.5 million grant to tease apart in the most comprehensive way ever devised the role of a single protein receptor in breast cells in cancer development and treatment. This protein determines which women will develop the most common kind of breast cancer and how she will fare during her treatment. The researchers' ultimate goal is to develop more advanced and better targeted therapies.
"We're combining the strengths of top scientists in this large-scale team science approach to achieve a new level of understanding of the estrogen receptor. That will allow us to make more meaningful predictions about clinical treatment of breast cancer and to be able to correctly identify new targets for therapy," says Robert Clarke, PhD, DSc, a professor of oncology and physiology & biophysics at Lombardi, and interim director of GUMC's Biomedical Graduate Research Organization. Clarke is the principal investigator of the new Center.
The National Cancer Institute (NCI) awarded the grant to Clarke and his team, which includes Leena Hilakivi-Clarke, PhD, professor of oncology at Lombardi; and Louis M. Weiner, MD, Lombardi's director. Georgetown joins ten other institutions across the United States to house a prestigious Center for Cancer Systems Biology.
"These centers represent a unique multidisciplinary union of outstanding scientists and clinicians who will work to unravel the complexities of cancer through the novel application of technology and mathematical modeling. Their discoveries and models will be critical to our continued success in understanding and treating this disease," said Dan Gallahan, PhD, program director for the NCI's Integrative Cancer Biology Program.
"This program is part of the next generation of cancer research, in that it will approach the disease from a holistic or comprehensive viewpoint in order to understand how all of the components of the disease fit together," said John E. Niederhuber, MD, NCI director.
Under the leadership of Howard Federoff, MD, PhD, executive vice president for health sciences at Georgetown, GUMC has rapidly moved into systems medicine, which is the application of systems biology to translation medicine with an ultimate goal of preventing or delaying illness, or managing it at the earliest stage possible. Both systems biology and systems medicine involve understanding a combination of factors, including genetics, lifestyle, environmental, that conspire to produce biological disorder.
In this grant, researchers at Lombardi will work with scientists at Virginia Tech and Fox Chase Cancer Center to understand how molecular signals from the estrogen receptor a protein in breast cancer cells that recognizes and binds the estrogen hormone and directs the cell's response to estrogen contribute to development and progression of breast cancer.
"We are so excited about this opportunity," Clarke says. "This is truly a systems approach to understanding a process that is fundamental to most breast cancer cases, and at the end of the day, we want to make things better for women with breast cancer."
The American Cancer Society estimates that in 2009, 192,000 women were newly diagnosed with invasive breast cancer, and approximately 70 percent of these cases are considered to be estrogen receptor-positive (ER+), implying that estrogen and its receptor drives the disease. Also in 2009, the Society estimated that more than 40,000 women are expected to die from breast cancer which is one breast cancer death on average every 13 minutes.
Most of the gene and proteins regulated by the estrogen receptor are unknown, and the molecular effects of therapies such as anti-hormonal drugs, like tamoxifen, are also largely unidentified, says Clarke. "This gene network ultimately regulates the choice of a cell to live or die in the face of stresses induced by endocrine therapies," he says.
To help understand the flow of signals from the estrogen receptor, Lombardi, Virginia Tech and Fox Chase Cancer Center will work as a collaborative team. Lombardi will focus on biology, examining cell cultures, mammary tumors in animals and patient breast tumors to decide ER+ molecular signaling systems, Virginia Tech scientists will build mathematical models to predict the behavior of those genes and proteins, and Fox Chase researchers will test what happens when specific genes and proteins are knocked out.
"Ultimately we will have a mathematical model to predict how the estrogen receptor system functions," Clarke says. "In the model, you can take out a gene and see how the system adjusts. That will allow us to identify good targets for therapy.
"Our part is to understand how breast cancer cells use the signaling from the estrogen receptor to survive and proliferate and make more copies of themselves and why in some tumors, you can block these signals with drugs, and they will die back, but then become resistant and grow back," says Clarke.
|Contact: Karen Mallet|
Georgetown University Medical Center