Introduction to the Center for Cancer Systems Biology

Breast cancer remains one of the most commonly diagnosed cancers in women. In the next 12 months, over 200,000 American women will receive a diagnosis of invasice breast cancer. Despite advances in early detection and treatment, over 40,000 women die of breast cancer each year in the U.S. Thus, on average one woman dies from breast cancer in the U.S. every 13 minutes.

 

Approximately 70% of breast cancers express the estrogen receptor (ER) protein. ERs bind the natural hormone extrogen and can cause many ER+ breast cancers to grow. Blocking this binding with drugs called antiestrogens (like Tamoxifen/Nolvadex®), or preventing the body from making estrogen using drugs called aromatase inhibitors (like Femara/Letrozole®) are effective treatments for many women. While aromatase inhibitors can be used only in postmenopausal women, antiestrogens can be used in premenopausal or postmenopausal women.

 

Overall, the benefits from these drugs are significant, e.g., Tamoxifen therapy can reduce the 10-year risk of death by almost one-third. For postmenopausal breast cancer patients, the benefits of Tamoxifen are as good as those for chemotherapy.

 

Despite these encouraging outcomes, not all women derive such a significant benefit from the antiestrogens or aromatase inhibitors. Many breast cancers that initially respond to therapy recur in later years, and these advanced (recurrent) breast cancers are very difficult to treat.

 

To address this critical problem, we have been funded by the National Cancer Center's Integrative Cancer Biology Program to create this new Center for Cancer Systems Biology (CCSB). We have done so by building upon existing collaborations among investigators at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, Fox Chase Cancer Center in Philadelphia, PA, and in the Departments of Biological Sciences and Electrical & Computer Engineering at the Virginia Polytechnic Institute and State University (Virginia Tech). Our multidisciplinary team comprises bioinformaticians, biostaticians, computer scientists, molecular biologists, endocrinologists, mathematicians, medical oncologists and medicinal chemists who already have a strong record of productive collaborations.

 

The central goal of our center is to understand, and then computationally and mathematically model, ER related activities that affect breast cancer susceptibility and responsiveness to antiestrogens and aromatase inhibitors. In doing so, we will discover new biomarkers to allow us to better define breast cancer risk and a breast cancer patient's prognosis and responsiveness to treatment. Since some of these biomarkers will also be new drug targets, our CCSB also includes a drug discovery initiative. While we will initially use newly discovered drugs as experimental reagents to test our computational and mathematical models, the most promising drugs will subsequently be developed as potentially new therapies for breast cancer. Consequently, the knowledge to be gained from our research should lead to significant improvements in the management of breast cancer risk and in the treatment of breast cancer.