Prostate Cancer Foundation 'beefs up' cancer research

The Prostate Cancer Foundation (PCF) has committed more than $19 million in new research funding for scientific investigations focused on discovering new treatments for recurrent prostate cancer. A total of eight programs representing 18 leading research institutions and 36 researchers were selected as part of the foundation's 2008 Challenge Awards. The funded programs will receive the first of three annual payments, ranging between $500,000 and $1.0 million per program, this week.

"We are very pleased to announce this year's recipients and believe their proposed projects will deliver critical contributions to the rapidly growing base of scientific knowledge on prostate cancer," commented Dr. Howard Soule, executive vice president of discovery and translation for the PCF. "These awards are aimed at accelerating breakthrough discoveries that can potentially end death and suffering from prostate cancer. That is our single focus and goal."

Designed to increase the impact of PCF funding, the PCF Challenge Awards invest in larger, multi-year projects with high potential for solving problems associated with advanced prostate cancer and that may lead to better treatments for this important men's health problem. The 2008 awards, selected in eight categories of scientific investigation, are:

1. Progression Biomarkers

Title: Clinical and Biological Insights into Prostate Cancer Derived from the Microfluidic Capture of Circulating Tumor Cells

Lead Investigator: Dr. Daniel Haber, Massachusetts General Hospital

The discovery of biomarkers that predict disease progression or provide a signal for effectiveness of an experimental medication for prostate cancer is a priority for PCF. These markers will increase the pace of new medication development and signal physicians earlier when prostate cancer is progressing. Dr. Haber, in collaboration with oncologists, biologists and engineers, will refine a system that measures tumor cells in patient blood. Enumeration of these cells provides an early signal of disease progression and will be clinically validated. Molecular evaluation of circulating tumor cells will be performed to better optimize prostate cancer therapy for individuals. Massachusetts General Hospital research team members: Dr. Richard J. Lee; Dr. Shyamala S. Maheswara; Dr. Sunitha Nagrath; Dr. Matthew R. Smith; Dr. Mehmet M. Toner.

2. ETS Gene Fusions

Title: Discovery of Inhibitors of TMPRSS2/ERG Function in Prostate Cancer

Lead Investigators: Dr. Levi A. Garraway, Dana-Farber Cancer Institute, Broad Institute; Dr. Todd R. Golub, Broad Institute of Harvard and MIT; Dr. William C. Hahn, Dana-Farber Cancer Institute, Broad Institute.

Scientists recently discovered that a specific genetic rearrangement in normal prostate cells leads to the production of cancer promoting factors (ETS factors) and prostate cancer. It is presumed that discovery of medications that block the activity of ETS factors will arrest the growth of prostate cancer. Dr. Golub will apply state-of-the-art genetic biotechnologies in a significant drug discovery effort to target ETS factors produced by prostate cancer cells. Collaborators at the Broad Institute of Harvard and MIT will work with biologists and oncologists at the Dana-Farber Cancer Institute and Harvard Medical School to evaluate ETS factor inhibitors discovered in this work and ultimately develop an experimental medication for prostate cancer patients.

3. Intracrine Androgens and Androgen Receptor Signaling

Title: Synergistic Targeting of AR and Androgen Metabolism in Prostate Cancer

Lead Investigators: Dr. Steven P. Balk, Beth Israel Deaconess Medical Center; Dr. Philip W. Kantoff, Dana-Farber Cancer Institute; Dr. Peter S. Nelson, Fred Hutchinson Cancer Research Center, University of Washington

For advanced prostate cancer patients, the best available treatment is the removal of testosterone hormones (androgens) that drive the growth and progression of prostate cancer. Medications that reduce androgens cause clinical remission invariably followed by disease progression. It is now known that androgens can be produced in tumor tissue, which is one cause for disease progression. Drs. Balk, Kantoff and Nelson will carefully study androgen reduction in tumor tissue from patients treated with a new generation of androgen production inhibitors and determine the mechanism of inhibition. Since it is likely that patients will ultimately become resistant to the new medications, identification of the mechanism of resistance will help identify the next generation of prostate cancer treatments. Research team members: Dr. Myles A. Brown, Dana-Farber Cancer Institute; Dr. Celestia Hignao, University of Washington; Dr. Paul Lange, University of Washington; Dr. Bruce Montgomery, University of Washington; Dr. Elahe Mostaghel, Fred Hutchinson Cancer Center; Dr. Trevor M. Penning, University of Pennsylvania; Dr. Mary-Ellen Taplin, Dana-Farber Cancer Institute.

4. Predictive Preclinical Models

Title: Consortium for the Development and Analysis of Relevant Prostate Cancer Model Systems

Lead Investigator: Dr. Robert L. Vessella, University of Washington

Laboratory models that reflect prostate cancer clinical biology are important for investigating new treatments for the disease. Dr. Vessella has organized a national consortium of expert investigators that intend to better characterize existing models of prostate cancer and determine where there are gaps in understanding clinical biology. The deficiencies will be corrected by creation of a new generation of models suitable for preclinical assessment of new, experimental medications for advanced prostate cancer. Research consortium members: Dr. Norman M. Greenberg, Fred Hutchinson Cancer Research Center, University of Washington; Dr. William C. Hahn, Dana-Farber Cancer Institute; Dr. Peter S. Nelson, Fred Hutchinson Cancer Research Center; Dr. Donna M. Peehl, Stanford University; Dr. Kenneth J. Pienta, University of Michigan Medical School; Dr. Hong Wu, UCLA.

5. Nutrition, Metabolism and Patient Quality of Life

Title: Prevention of Treatment and Disease-Related Morbidity During Androgen Deprivation Therapy: A Multi-Center Proposal

Lead Investigator: Dr. Matthew R. Smith, Massachusetts General Hospital Cancer Center

The best available treatment for advanced prostate cancer is the removal of testosterone hormones (androgens) that drive the growth and progression of prostate cancer. However, the medications used to reduce androgen in patients with advanced prostate cancer cause significant secondary illness. Dr. Smith and his U.S./Canada team of investigators plan to study the health consequences of androgen reduction and will determine medical interventions to prevent the negative consequences of treatment. This expert team will determine how to limit obesity, diabetes, bone fractures and heart disease in patients treated for advanced prostate cancer. Exercise, nutrition and new medications will be employed to enhance the health of these patients with advanced prostate cancer. Research team members: Dr. Stephen J. Freedland, Duke University Medical Center; Dr. Nancy L. Keating, Harvard Medical School; Dr. David M. Nathan, Massachusetts General Hospital; Dr. Michael A. Pollak, McGill University/Jewish General Hospital.

6. Epigenetics

Title: Epigenetic Strategies in Androgen Receptor-Dependent Interchromosomal Networking and Translocation

Lead Investigator: Dr. Michael G. Rosenfeld, University of California, San Diego

Epigenetics is a relatively new area of cancer biology that describes genetic regulation which is independent from DNA sequence. Cancer occurs due to both mutation and epigenetic alterations resulting in dysregulation of growth control. Only recently have scientists discovered epigenetic changes in tumor cells that can be controlled with new medicines. Dr. Rosenfeld and his expert team propose the application of a new genetic biotechnology to discover genetic and epigenetic changes resulting in prostate cancer. The overall goal of this work is the discovery of new medications that control prostate cancer when all existing treatments have failed. Research team members: Dr. Xiang-Dong Fu, University of California, San Diego; Dr. Sheng S. Ding, The Scripps Research Institute.

7. Immunotherapy

Title: CTLA-4 Blockade in Therapy of Prostate Cancer: Therapeutic Mechanisms and New Directions

Lead Investigator: Dr. James Allison, Memorial Sloan-Kettering Cancer Center and Dr. Padmanee Sharma, M.D. Anderson Cancer Center

Immunotherapy is a treatment for cancer that involves directing a patient's immune response against their cancer to cause elimination of the tumor. A variety of immunotherapeutic strategies for the treatment of prostate cancer are under development. There is a significant need for discovery of blood markers that will herald an anti-tumor response as well as warn of an impending adverse event due to the therapy. Drs. Sharma and Allison are performing clinical evaluation of advanced immunotherapies. They plan to perform a rigorous molecular analysis of the patient response to immunotherapy for treatment of prostate cancer. The goal is to use these findings to develop more effective and safer immunotherapeutic treatments for prostate cancer. Research team member: Dr. Neal R. Rosen, Memorial Sloan-Kettering Cancer Center.

8. Prostate Cancer Stem Cells

Title: Defining Targets and Biomarkers in Prostate Cancer Stem Cells: New Therapeutic Opportunities

Lead Investigator: Dr. Owen N. Witte, UCLA

Cancer stem cells are an elusive, small subpopulation of tumor cells that are not only resistant to therapy but also repopulate a solid tumor after most tumor cells are killed by a therapy. Understanding the biology of cancer stem cells and targeting their elimination is a priority in cancer research. Dr. Witte and his team at UCLA and the Salk Institute of Biological Studies are world leading experts in cancer stem cell biology. This team will now direct their expertise toward studies of prostate cancer stem cells. Application of new genetic biotechnologies will better define this critical tumor cell population and will reveal therapeutic targets. Research team members: Dr. Pei-Yu E. Chiou, UCLA; Dr. Isla P. Garraway, UCLA; Dr. Michael A. Teitell, UCLA; Dr. Hong Wu, UCLA; Dr. Inder M. Verma, The Salk Institute.

"The focus of our three-year Challenge Awards is to fund teams that 'challenge' the idea that advanced prostate cancer is incurable. Without PCF funding, these teams would not have the necessary resources to move their work forward," explained Dr. Jonathan Simons, President, Chief Executive Officer and David H. Koch Chair for the Prostate Cancer Foundation. "The applicant teams proposed new hypotheses and approaches in biotechnology that could significantly reduce prostate cancer deaths. We were pleased to receive a record 113 research team proposals from 105 cancer programs in 11 countries.

"We are profoundly grateful to translational research experts who rigorously reviewed this high tide of proposals, so we could then fund the top teams in less than 100 days," added Simons. "Patients and families can find hope in the breadth and depth and innovation in prostate cancer research in 2008. It is now a global activity."

Recipients of PCF Challenge Awards were chosen by an expedited peer review committee of 52 skilled scientific and clinical experts. Specific milestones are outlined by the foundation for yearly review, and research teams are required to share their findings at the PCF annual Scientific Retreat. A complete list of the peer review team members can be found at www.prostatecancerfoundation.org/challenge-awards/review.

About the Prostate Cancer Foundation

The Prostate Cancer Foundation (PCF) is the world's largest philanthropic source of support for prostate cancer research. The foundation's primary goal is to discover better treatments and a cure for recurrent prostate cancer. PCF pursues its mission by reaching out to individuals, corporations and others to harness society's resources--financial and human--to fight this deadly disease that strikes one out every six men.

Founded in 1993, the PCF has raised more than $350 million and provided funding to more than 1,400 researchers at nearly 150 institutions worldwide. The foundation has been a pioneer in the grant making process, simplifying paperwork for grantees and leaving more time for researchers to conduct needed scientific research. The PCF also advocates for greater awareness of prostate cancer and more governmental resources, resulting in a 20-fold increase in government funding for prostate cancer.

http://www.prostatecancerfoundation.org