Prostate Cancer Research
The Prostate Cancer Foundation has been a major catalyst for many of the scientific advances in prostate cancer research since 1993. PCF has awarded more than 2,000 projects that offer hope for improving outcomes in patients with prostate cancer. These high-impact projects include clinical research to evaluate new drugs, novel treatment strategies for prostate cancer and basic science research to better understand the biology of prostate cancer.
PCF grant funding has led directly to many advances in comprehending the underlying mechanisms of prostate cancer, including identification of the genetic changes that might cause cells in the prostate to become cancerous; interference with the development of blood vessels that feed nutrients to cancer cells; identification of prostate cell surface markers that can be targeted to destroy cancerous cells; and development of analytical methods that identify the proteins in blood or the prostate that correlate to treatment effect or behavior of the cancer cell.
At the same time, the Prostate Cancer Foundation has funded key clinical trials as part of its efforts to shorten the time between drug development and FDA approval. Since 1993, the PCF has funded the discovery and/or early clinical development of such diverse agents as monoclonal antibodies that directly target prostate cancer cells, bisphosphonates for the prevention and treatment of bone metastases, and endothelin-A receptor antagonists. Importantly, six of the nine new drugs for prostate cancer patients that have gained FDA approval since 2002, were supported by PCF-funding at some point during their discovery or development. Each of these agents is poised to make a significant impact on the outcomes of patients with prostate cancer.
The following discoveries were all made by Prostate Cancer Foundation-supported scientists:
Genetics – Drs. Kathleen Cooney, MD, at the University of Michigan, and William Issacs, PhD, at Johns Hopkins, made the first-ever discovery of an inherited mutation associated with increased risk for developing prostate cancer. Assessment of this gene, HOXB13, will allow identification of men with significantly increased risk for developing prostate cancer and generate new insights into disease biology.
Biomarkers – Drs. Scott Tomlins, MD, PhD, and Arul Chinnaiyan, MD, PhD, of the University of Michigan, developed a non-invasive, highly specific urine test that predicts the presence of clinically relevant prostate cancer in men with elevated PSA levels. TMPRSS2:ERG is a prostate cancer-specific chromosomal fusion that occurs in ~50% of prostate cancers, and was first discovered by these researchers. PCA3 is gene that is highly expressed by prostate cancers. This test, Mi-Prostate Score (MiPS), detects the RNA of TMPRSS2:ERG and PCA3 in the urine, and incorporates the results with PSA levels, for enhanced stratification of a patient’s risk of having aggressive prostate cancer, which may help men to avoid unnecessary biopsies and procedures. The MiPS test is now commercially available from the University of Michigan MLabs.
Targeted Therapies – Drs. Howard Scher, MD, of Memorial Sloan-Kettering Cancer Center, and Johann de Bono, MD, PhD, of the Royal Marsden Hospital, UK, led efforts in organizing the phase III clinical trials that resulted in FDA approval of two new therapies that target different aspects of androgen receptor activity, enzalutamide (Xtandi) and abiraterone acetate (Zytiga), for use in patients with metastatic castrate-resistant prostate cancer. Ongoing clinical trials are testing the efficacy of these drugs at different stages of disease, and in combination with various other treatment modalities.
Targeted Therapies – Drs. William Polkinghorn, MD, of Memorial Sloan-Kettering Cancer Center, and Karen Knudsen, PhD, Thomas Jefferson University, both discovered the reason that androgen-deprivation therapy and ionizing radiation are synergistic in the treatment of prostate cancer patients: the androgen receptor directly activates genes that repair DNA, so unless the androgen receptor is inhibited, prostate cancer cells can more easily resist death caused by radiation – which is due to DNA damage. Multiple clinical trials testing drugs targeting DNA-repair proteins (PARP1) in prostate cancer, led by PCF-funded researchers are ongoing, and trials with drugs targeting other DNA-repair proteins are being planned.
Targeted Therapies – Drs. Felix Feng, MD, and Maha Hussain, MD, of the University of Michigan, are leading first-in-field clinical trials to test the efficacy of combining a drug targeting a cancer cell growth regulator, CDK4/6 (PD-0332991), with androgen deprivation therapy (bicalutamide). Expression of the Retinoblastoma (Rb) protein by prostate cancer cells may predict which patients will respond to this therapy and is being assessed as part of these trials.
Exercise – Dr. Lorelei Mucci, ScD, of the Harvard School of Public Health, has discovered a potential reason why energetic physical activity increases survival time in men diagnosed with prostate cancer. Regular brisk walking (>3 mph) was associated with more normally shaped blood vessels in prostate tumors, a factor shown to lower the risk of lethal disease. This study emphasizes how regular exercise directly benefits prostate cancer patients.
Nutrition – Drs. June Chan, ScD, and Stacey Kenfield, ScD, of the University of California, San Francisco, found that dietary intake of vegetable fats reduced the risk of progressing to lethal prostate cancer in men who had been diagnosed with nonmetastatic prostate cancer. Higher consumption of carbohydrates and animal fats was associated with increased risk of progression to lethal disease. Certain types of dietary fats may prevent vs. enhance prostate cancer progression.
Prevention - Dr. Elizabeth Platz, ScD, of the Johns Hopkins Bloomberg School of Public Health, discovered that men who took statins significantly cut their risk of developing advanced prostate cancers, particularly metastatic and lethal cancers, by half or more. The risk of developing indolent cancers however, was unaffected. Statins are commonly prescribed cholesterol-lowering medications used to prevent heart attacks and strokes. These studies indicate that statins may prevent the progression of prostate cancers from indolent to clinically relevant lethal disease states.