FIFTEEN YEARS OF PROGRESS
Leveraging Resources Accelerating Discovery Inspiring Hope 2007 Progress Report
The Prostate Cancer Foundation (PCF) was founded in 1993 to find better treatments and a cure for recurrent prostate cancer. Through its unique model for soliciting and selecting promising research programs and rapid deployment of resources, the PCF has funded more than 1,500 programs at nearly 200 research centers in 20 countries around the world. As the world’s leading philanthropic organization for funding prostate-cancer research, the PCF is now a foundation without borders. Its advocacy for increased government and private support of prostate cancer programs has helped build a global research enterprise of nearly $10 billion. In 2007, 30 percent fewer men in the U.S. died from prostate cancer compared for more to what was once projected. The PCF is a force of than 16 million men and their families around the world who are currently facing the disease.
We have turned the corner. We will not give up. An end to death and suffering from prostate cancer is in sight.
Ta b l e o f C o n t e n t s
Founder/CEO Letter Research Highlights Top Transformational Discoveries New Strategies for Accelerating Discovery Donors Roll Appeal for Support Donation Opportunities Financial Statements Report of Independent Auditors Board of Directors and Leadership Team
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Cover Photos: The PhIP carcinogen molecule (yellow), damaging a DNA helix. PhIP, formed by charring meats at high temperatures, can insert itself into DNA, causing errors in reading and replicating DNA. This can result in mutations that contribute to prostate cancer formation. Image from the diet and prostate-cancer genetics research led by William G. Nelson, M.D., Ph.D., (pictured in the lower right) at the Johns Hopkins Medical Institutions. The discovery of PhIP as a major carcinogen of prostate cancer – the potential equivalent of cigarette smoking in lung cancer – was made through PCF-supported research. Read about the scientific innovations of other PCF-funded researchers including Christopher Logothetis, M.D., University of Texas M.D. Anderson Cancer Center (lower left), Robert Getzenberg, Ph.D., Johns Hopkins (upper left), and Robert Langer, Sc.D., at MIT (upper right) in this report.
Turning the Corner: Dear Friends, Fifteen years ago, the Prostate Cancer Foundation (PCF) was formed to discover better treatments and, ultimately, a cure for prostate cancer. We believe attainment of this goal is now within sight. From the start, we understood that progress would not only require basic funding of prostate-cancer research, but a comprehensive re-engineering of the processes that support it. We developed an innovative model for rapid solicitation and review of research proposals, and accelerated deploy ment of funding. Our grant recipients were required to share their data on a regular basis to stimulate scientific exchange and speed discovery. We also committed to a strong advocacy program for promoting government and private
15 Years of Progress for Prostate Cancer Research to $550 million from $27 million – a more than twenty-fold increase; the number of dedicated research labs has grown from just three to more than 200; 18 nations now have prostate-cancer research centers, up from three; and once non-existent tissue banks now contain more than 20,000 samples for crucial scientific experiments. 2. Scientific discovery is accelerating. Back in 1993, there were no promising new drugs in the development pipeline. Today there are more than 20 new therapies in development and more than 60 new types of clinical trials each year. The number of published research articles on prostate cancer published last year reached 36,000 compared to 2,500 when the PCF was founded.
investment in prostate-cancer research and public awareness
3. Lifestyle changes capable of slowing disease
of the disease.
progression are emerging. PCF funding has
The foundation’s leadership has leveraged every dollar many times over. Through the work of the PCF, and the efforts of its strategic partners around the world – medical institutions, government organizations, other foundations and private companies – prostate cancer has expanded from a neglected specialty to one of the most vibrant areas of biomedical research. Today’s global research enterprise for prostate cancer represents nearly $10 billion in investments. During the past fifteen years, PCF-supported research has made a profound difference in the lives of prostate cancer patients and medical professionals treating this disease. Consider these accomplishments:
stimulated some of the most rigorous nutrition and diet research of any cancer research funding agency during the past 15 years. From our inception, we have been interested in the link between lifestyle factors (diet and exercise) and their effect on the occurrence and growth of prostate cancer. This area of investigation is one of our eight key areas of funded research. More than 850 papers have now been published on nutrition and prostate cancer, and $20 million is allocated annually by funding and research organizations for cancer-related nutrition research. 4. Most importantly, fewer men are dying. PCF-funded science, our advocacy for increased public funding, and heightened public awareness of prostate cancer
1. Prostate cancer has expanded from a neglected
has resulted in fewer men dying from the disease. In 1995,
specialty to one of the most significant areas of
the American Cancer Society projected 40,000 deaths
biomedical research. As a result of our advocacy, U.S.
from prostate cancer in 2007. The reality was 28,000 –
federal funding for prostate-cancer research has increased
a reduction of 30 percent. We will continue this progress. 1
As we proceed, we will be able to build on our expanded
adversely affect the return on our investments to date and
base of prostate-cancer knowledge. PCF-funded researchers
put scientific progress at risk.
will gain a deeper understanding of the multiple molecular contributions to prostate cancer and develop more effective and targeted drugs for every stage and type of the disease. They will develop enhanced diagnostic and prognostic tools that will better indicate which treatments are best suited to particular patients, and explore new, science-based
To realize our shared goal of eliminating prostate cancer, we need your ongoing commitment. Give us the tools – in the form of your continued financial support – and we will finish the job. Sincerely,
preventive approaches. The progress to date has been possible largely because of the foundation’s collaborative and multi-disciplinary model of science, our innovative reforms to traditional grant processes and funding strategies. The PCF Inspires HOPE Our progress inspires hope for millions of prostate cancer patients and their families around the world. This hope is born of the commitment of the diverse PCF community: talented, innovative researchers; patients, survivors and their families; our corporate partners; and far-sighted venture philanthropists, who believe they will
Jonathan Simons, MD
achieve the best possible return on investment in prostate-
Founder and Chairman
President and Chief Executive Officer David H. Koch Chair
cancer research. The following pages describe three major research projects we funded in 2007 and the top ten transformational discoveries in prostate cancer achieved through PCF funding. There is also a complete discussion of our new funding program. Finally, in 2007, the PCF raised a record amount to fund crucial research programs that would not have been otherwise funded. While we’re determined to reach our goal and end the devastation caused by prostate cancer, U.S. federal funding for advanced cancer research, in real dollars, is declining for the first time in 15 years. Throttling back on the flow of research dollars now will 2
research Highlights In 2007, our fast-track approach to supporting scientific progress for prostate cancer continued. While committing funding for more than 86 research initiatives, we also conducted an extensive review of our Competitive Research Awards program. More than 40 prostate-cancer researchers participated in the ten-month review. As a result, we outlined a three-pronged research funding approach to advance the agenda of the PCF through 2012.
Advancing Research Models The PCF Prostate Cancer Models Working Group, comprising 13 former PCF competitive-award recipients from 12 institutions, met intensively at the PCF and published State of the Science on Current Research Models in Prostate Cancer. This effort was conducted as a public service and provides a comprehensive point of reference for testing new drugs. The report is a “state of the science” of all prostate-cancer research models that was made available for university scientists and pharmaceutical and biotechnology investigators who want to enter the field of prostate-cancer research. Underscoring the PCF’s support of ahead-of-the-curve science, many of the new models forwarded by the team will be incorporated into drug and diagnostics development by the biotechnology and pharmaceutical industries, as well as by the broader scientific community working on prostate cancer. Most importantly, PCF-funded researchers continued to make scientific breakthroughs in the development of new prostate-cancer treatments.
Three Novel Research Programs Funded by the PCF 1. Nanotechnology-based Solutions Nanotechnology, involving materials smaller than 100 nanometers (the size of atoms), holds enormous promise for cancer research and patients. At this scale, materials exhibit unique characteristics and properties, making the use of nanoparticles a promising area for cancer detection, diagnosis and treatment. We are funding the world’s leading team in nanoparticle delivery of prostate cancer medicines. The team is led by Robert Langer, Sc.D., at MIT and Omid Farokzhad, M.D., at Brigham and Women’s Hospital. This project is exploring if nanoscale particles can act as Trojan horses in the body, delivering medication directly to prostatecancer cells while bypassing healthy cells.
Logothetis, M.D., University of Texas M.D. Anderson Cancer Center; Kenneth Pienta, M.D., University of Michigan; and Robert Vesella, Ph.D., University of Washington.
3. Turning the Heat Up on Prostate Cancer
Acting like Trojan horses in the body, targeted nano particles show potential for delivering anti-cancer compounds directly into prostate cancer cells while avoiding healthy cells.
Subsequently, MIT team members received a special additional $650,000 Amplification Award from the PCF for the early completion of milestones outlined as part of the KochPCF Nanotherapeutics Challenge Award. Other team members are Philip Kantoff, M.D., Dana-Farber Cancer Institute, and Neil Bander, M.D., at Weill Medical College/Cornell University.
2. Co-Targeted Drug Therapies: Hitting Two Achilles Heels at One Time Because few agents have been approved or are currently in clinical trials for the prevention and treatment of bone metastases in men with prostate cancer, there is a great need for better treatment strategies. One approach is to combine drugs with different mechanisms of action. Sometimes it takes two or more drugs working together to kill a prostate-cancer cell and innumerable drug combinations are possible. What’s needed is a way to prioritize possible drug combinations based on rigorous pre-clinical evaluation. This two-year program will focus on evaluating combinations of drugs already available for clinical trials in animal models. The team of primary investigators for this PCF-funded project includes: Theresa Guise, M.D., University of Virginia; Christopher
During the past two decades, systematic treatment with cytotoxic drugs or radiation therapy has cured some advanced, metastatic cancers, such as testicular cancer. In spite of these successes, no molecular targets have yet been identified to explain these therapeutic successes. This PCF program will focus on learning about “what worked” in testicular cancer because – even with extensive and advanced metastasis to the brain and lungs – the vast majority of these patients are now successfully treated with systemic therapy and restored to long-term normal health. Lance Armstrong, who went on to win the Tour de France seven times, is one such patient. An extensive analysis of scientific literature indicates strong evidence that metatastic testicular tumor cells experience abnormal thermal (heat) stress when subjected to normal body temperatures. The result is a heightened response to therapy by cytotoxic drugs, radiotherapy and immunotherapy. The team will explore the possibility of directing heat only to cancer cells using tumor-selected nanoparticles that can be heat-controlled by noninvasive external energy sources such as magnetic fields. This project is designed to be a highly interactive program with expertise from five institutions including MIT, DanaFarber Cancer Institute, the University of Michigan, Johns Hopkins University and The Prostate Cancer Center–Vancouver. The Integrative Operational Coordinators are Robert H. Getzenberg, Ph.D., and Theodore L. DeWeese, M.D. of The Johns Hopkins University School of Medicine.
Top Transformational Discoveries in Prostate-cancer research in 2007 The impact of scientific discoveries can be measured partly by the number of times a discovery is cited by other scientists who use the findings to push forward their own research. As a way of “keeping score,” the more a discovery is used by other cancer scientists, the more important it is. Cited by peers and selected for presentation of papers to annual American Association for Cancer Research meetings, the nine discoveries described below have transformed the field of prostate-cancer research in 2007. Each of these discoveries is a direct result of the PCF funding a high-impact/high-risk research idea through its Competitive Awards Program. 1. Genetics – William B. Isaacs, Ph.D., at Johns Hopkins and Xiangfeng Xu, Ph.D., of Wake Forrest University discovered regions of DNA in the human genome that can predict a ten-times higher lifetime risk for prostate cancer. Once this is confirmed in broader populations, a simple saliva test or blood test could provide a useful predictive test for men with a family history of prostate cancer. For sons and grandsons of fathers who carry genes for prostate cancer, this could become a lifesaving test. Dr. Isaacs has been a recipient of PCF Competitive Research Awards since 1995. 2. Activating the Immune System Against Prostate Cancer – Eugene Kwon, M.D., at the Mayo Clinic, identified three new “brakes” in the male immune system that prevent a patient’s immune system from seeing and attacking prostate cancer. These brakes must be lifted for the patient’s immune system cells to “see” the prostate cancer as a foreign invader and eradicate it. The “brake” (B7H3) may be released using new therapeutic agents that could block the function of B7H3. This discovery opens the door for developing new drugs to awaken proper immune responses. 3. A Better “Detector Test” for Prostate Cancer – Robert Getzenberg, Ph.D., at Johns Hopkins University, has discovered that a protein called EPCA-2 is a novel biomarker associated with prostate cancer and that it is detectable in the blood. The PSA test detects prostate diseases including prostate cancer but is not specific to prostate cancer. Many patients undergo biopsies with an elevated PSA blood test that do not have prostate cancer. In contrast, EPCA-2 is produced only by prostate cancer cells. If it is found in the blood it means cancer is present. EPCA-2 also has sensitivity and specificity, enabling it to differentiate between men with organ-confined and non-organ-confined disease. Dr. Getzenberg has been a recipient of PCF Competitive Research Awards since 2005. As a result of this proteomics discovery in prostate cancer, patients and doctors may soon have an effective new blood test for initial detection and subsequent monitoring of EPCA-2 to follow remissions after treatment. 4. Targeted Therapies – Arul Chinnaiyan, M.D., Ph.D., and his colleagues at the University of Michigan, discovered an “on-switch” – a case of a chromosomal translocation and fusion of two unrelated genes (TMPRSS2 and ERG) that is unique to prostate cancer. The finding has garnered multiple research prizes and unearthed an entire new way of understanding how prostate cancer is “turned on” in normal cells. The ERG gene itself is now indicated as a key gene to block with targeted medicines. The team is now developing a system to screen hundreds of molecules that might inhibit activity of ERG. Further, because the fusion of these genes is detected easily and unique to prostate cancer, they are good targets for cancer-killing therapies that could destroy prostate cancer cells without damaging healthy cells. Research is also underway to develop a simple urine test to detect prostate cancer earlier than PSA does by detecting the chromosomal fusions. For patients, this is a landmark molecular finding that can guide precisely which treatments are best matched for them. Dr. Chinnaiyan has been a recipient of PCF Competitive Research Awards since 2001.
5. STAT5 A New Target for Drug Therapy – Edward Gellmann, M.D., at the Columbia University Medical Center identified a new path linking the STAT5 “inflammatory pathway” gene to the action of androgen receptors in hormone-resistant prostate cancer. STAT5 is a key molecule involved in normal inflammation and tissue-wound repair. In hormone-resistant prostate cancers it is “hijacked” and can replace or boost testosterone action on androgen receptors. This enables hormone-resistant cancer cell clones to survive and grow. New drugs targeting STAT5 are now a compelling research area for co-targeting research. Dr. Gellman has received PCF Competitive Research Awards since 1994. 6. Biomarkers of Metastatic Disease – A key genetic change in prostate cancer is the loss of the PTEN gene that may be involved with metastasis. PTEN-mutated prostate cancers are responsible for many deaths from prostate cancer each year. Charles Sawyers, M.D., at Memorial Sloan-Kettering Cancer Center, discovered a marker in the blood known as Insulin Growth Factor Binding Protein 2 that is associated with PTEN-mutated tumors. For patients, this could mean earlier diagnosis of metastatic disease activity in the bone. Starting treatment earlier (compared to bone scans) could be a large therapeutic advance in some patients. An analytic blood test that employs a proteomics-based technology to detect microscopic cancer growth is possible given this finding. Dr. Sawyers has received PCF Competitive Research Awards since 1996. 7. Nutritional Sciences – William Nelson, M.D., Ph.D., at Johns Hopkins, discovered that a major carcinogen (PhIP) found in charred, grilled meats appears to accumulate in the area of the prostate that later develops prostate cancer. PhIP has the same DNA mutational capacity as cigarette smoke but the carcinogen accumulates only in the prostate. This finding has triggered major new studies on the healthiest way to cook meats in order to protect the prostate from accumulating carcinogens over a lifetime. Ultimately, further research into why PhIPs accumulate in the prostate may change dietary recommendations, help reduce the incidence of prostate cancer and protect men from prostate cancer starting at an early age. Dr. Nelson has been a PCF Competitive Research Award Recipient since 1993. 8. Intracrine Androgens – Peter Nelson, M.D., and Elahe Mostagel, M.D., Ph.D., at the Fred Hutchinson Cancer Research Center and the University of Washington, determined that not all patients undergoing hormone therapy may achieve full suppression of androgens. Some tumor microenvironments may create survival testosterone chemically from normal cholesterol. In 50 years of research on testosterone in prostate cancer biology, this possibility was not scientifically tested until Dr. Nelson and his colleagues conducted these studies. The development of new therapeutic agents to block this “intracrine androgen” could benefit more than 50,000 U.S. men annually whose tumors are resistant to current hormonal therapies. Dr. Nelson has been funded by PCF Competitive Research Awards since 1999. 9. Antioxidants and Prostate Health – Oxidation damages biological molecules and causes prostate cancers. Consumption of foods rich in antioxidants, if those antioxidants can leave the stomach, enter the bloodstream and penetrate the prostate, may counteract oxidative stress and provide beneficial effects against cancer. David Heber, M.D., Ph.D., at UCLA, demonstrated that several large antioxidant molecules called polyphenols exist in strawberries. Whole strawberry extract and the individual polyphenols isolated from strawberry extracts slowed proliferation of prostate, oral and colon cancer cell cultures. Response to purified polyphenols is dose-dependent and related to the antioxidant activity of each compound. A new science is emerging for prostate cancer prevention that views components of foods scientifically and as agents that may reduce the incidence of prostate cancer. Dietary recommendations and rigorous studies of which compounds and supplements should be incorporated into the diet is emerging. These dietary recommendations may be particularly important to the men carrying genes for prostate cancer. Dr. Heber has been a recipient of PCF Competitive Research Awards since 1994.
New Strategies for Accelerating Discovery PCF Competitive Awards, introduced in 1993, revolutionized the way research is evaluated and funded, empowering many young scientists to fill the pipeline of innovation with new diagnostic and therapeutic tools. This model has proven enormously successful: There is virtually no new scientific idea or product in development or on the market for prostate cancer that has not been supported at least in part by PCF funding. As a direct result of our support and advocacy, the scientific and medical community has turned the corner on prostate cancer. We believe an end to death and suffering from this disease is in sight. To ensure that we ultimately attain our goal of eliminating death from prostate cancer, we conducted a comprehensive review of our competitive awards programs from 1993 to 2006. While the review concluded that the awards program performed exceedingly well
and fulfilled our initially-stated 1993 goals, we decided to develop a new strategy to build upon the initial success. More than 40 prostate-cancer research experts and experts in biotechnology were involved in developing the new strategy. By the end of 2007, we introduced a strategy designed to focus on specific assets in the field of prostate-cancer research. It will build a sustainable and dynamic research enterprise comprising cross-disciplinary teams working on multi-year programs and drive our efforts to develop new, effective therapies for eradicating this disease. The resulting funding programs are designed to replace our former Competitive Research Awards Program. Each of the programs is unique with individual goals and objectives designed to integrate with each other and, most importantly, to be scalable and self-perpetuating.
PCF Research Enterprise 2007/2008
Human Capital Initiatives
“First-in-Man” Therapeutic Clinical Investigation
Prodigy Awards (3)
Individual Investigators (25)
2008 Challenge Awards
3-year $450,000 investment Recognition Awards (4) (Scientific meetings)
$40,000 annual investment 2008 PCF Young Investigator Awards
3-year $4,700,000 investment
$2,500,000 annual investment
3-year $20,100,000 investment Progression Biomarkers Discovery and Validation Intracrine Androgens and Androgen Receptor Signaling Nutrition, Metabolism and Patient Quality of Life ETS Gene Fusions Prostate Cancer Stem Cells Epigenetics Immunotherapy Predictive Preclinical Models
2007 Special Challenge Programs
5-year $12,100,000 investment* EPCA-2 Biomarkers Research & Development *OHNS (OPKINS 5NIVERSITY
Koch PCF Nanotherapeutics -)4(ARVARD#ORNELL
PCF Safeway S.T.A.R. Program: Thermal Enhanced Metastatic Therapy *OHNS (OPKINS 5NIVERSITY
Prostate Cancer Genomics 4RANSLATIONAL 'ENOMICS 2ESEARCH )NSTITUTE
Proteomics Technology Development 3PIELBERG &AMILY