The Breast Cancer and Prostate Cancer research programs have now been combined into the Hormone Responsive Cancers program.
Malignancies of the reproductive system are a major cause of morbidity and mortality. Breast cancer and prostate cancer are the most common malignancies in women and men, respectively. Furthermore, major disparities exist in the incidence and outcome of these diseases in different populations. It is imperative to provide innovative approaches to diagnosis, treatment, and prevention of these diseases. The Hormone Responsive Cancers program addresses these goals through translational research. Many projects are directed towards the identification of novel or overexpressed molecules that can serve as new biomarkers, aid in diagnosis, improve existing treatments and function as targets for novel therapies.
The HRC program has five major focus areas:
Highlights of the Hormone Responsive Cancers research program include the following:
Aromatase inhibitors to block estrogen synthesis were developed in this program.(Read an interview with Dr. Angela Brodie about her discovery of this new class of drugs.) These agents are now used for both prevention and treatment of breast cancer. Novel androgen inhibitors for treatment of prostate cancer have been discovered and are being advanced to clinical trials.
Novel compounds have been identified that inhibit retinoic acid metabolism and appear to be promising agents for breast cancer therapy. Based on original discoveries from this program, studies are in progress to enhance MRI with spectroscopic measurements of citrate to identify areas of malignant prostate in patients. Two laboratories have identified novel proteins (EBP1 and PCDGF) that are overexpressed in breast cancer and in collaboration with the Experimental Therapeutics Research Program, lead compounds have been identified that target one of these. Cyclooxygenase expression is linked to more aggressive behavior in breast cancers and inhibitors are being evaluated in preclinical studies.
Studies of tumor-vascular biology are being conducted in three laboratories. Computer-assisted drug design has been employed to identify candidate therapeutic compounds and effective gene therapies are being developed to inhibit tumor angiogenesis.
Mechanisms of drug resistance are being elucidated and strategies developed to circumvent resistance to activation of alternative signaling pathways and apoptosis induction. Two immune-based therapies using vaccination to tumor-associated antigens have been developed in preclinical models and are now in early clinical trials.
Initiatives to understand the biology of tumor invasion and metastasis are examining the role of cytoskeletal components in cell motility and the role of proteases in invasion.
A Center of Excellence joint program of HRC Program members and investigators at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center is identifying genes associated with breast cancer metastasis and developing therapeutic agents to these new targets.
HRC program members and members of the Cancer Disparities and Intervention Research Program (CDIRP) are studying the factors affecting breast and prostate cancer disparities including differences in drug and citrate metabolism and gene expression patterns in diverse populations.