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Prostate Cancer Foundation Issues $4.5 Million in Grants to Support Innovation From Young Investigators

2010 Press Release

Awards Go to 21 Young Research Scientists to Accelerate New Discoveries for Battling Prostate Cancer

SANTA MONICA, CA/April 13, 2010 -- The Prostate Cancer Foundation (PCF) today announced the funding of 21 new Young Investigator Awards at 17 leading cancer centers in the U.S. and Canada. Designed to encourage the most innovative minds in cancer research to focus their careers on prostate cancer, the awards provide recipients with three years of funding to test transformational research questions for prostate cancer patients. The 2010 Young Investigator Awards represent a new $4.5 million investment in the global cancer research community by PCF.

With the announcement of the 2010 Young Investigators, PCF is now funding 43 research projects led by young investigators around the world. These Young Investigator projects are three years in duration. Each award is $225,000 total and is matched dollar for dollar or matched in kind by the recipients’ research institutions, making the total award worth $450,000 in support.

“We are investing in the careers of the world’s ‘best of the best’ in computer science, molecular biology, pharmacology, radiation oncology, medical oncology and endocrinology to answer the challenge of discovering better treatments and cures for prostate cancer,” commented Howard R. Soule, PhD, executive vice president and chief science officer for PCF.

“The research mentors of these Young Investigators are as expert, accomplished and committed as we have ever seen,” said Jonathan W. Simons, MD, president and CEO of PCF. “We look forward to seeing the contributions these young scientists will make in our field.”

The 2010 PCF Young Investigator Award recipients are:

The LeFrak Family – PCF Young Investigator Award

Himisha Beltran, MD

Weill Cornell Medical College – New York, NY

Dr. Beltran’s research will help define the genetic basis of a rare and aggressive form of prostate cancer called neuroendocrine (small cell) prostate cancer (NEPC). Patients diagnosed with NEPC often have Gleason 9 or 10 types and an average survival of less than two years. These men are often under 50 years old at diagnosis as well. It is currently unclear how this type of prostate cancer is initiated, and why it so often resists standard therapies for advanced prostate cancer. The characteristics of NEPC clones are very different from the more common prostate cancer type: adenocarcinoma. Determining the genetic differences specific to NEPC should enable the development of new biomarkers and targeted therapy for this exceptionally aggressive form of the disease.

PCF Young Investigator Award in Honor of Our Soldiers and the Department of Defense Congressionally Directed Medical Research Program for Prostate Cancer

Justine Bruce, MD

University of Wisconsin Carbone Comprehensive Cancer Center – Madison, WI

New therapeutics are urgently needed for hormone resistant prostate cancer when it emerges. Some patients with evidence of metastatic disease may receive chemotherapy while the same therapy for asymptomatic patients may be delayed. Dr. Bruce is interested in developing new targeted medicines for a large population of patients that show no evidence of metastatic disease, but whose PSA continues to rise following hormonal treatment. This clinical situation is called a hormone resistant biochemical recurrence, and over 20,000 US men are in that situation at any given time. A novel experimental agent, TRC105, which is under clinical investigation at a biotechnology firm named Tracon, may hold promise for patients with advanced disease. TRC105 is a monoclonal antibody against the endoglin protein found on the surface of tumor blood vessel cells. TRC105 blocks the proliferation of vascular cells required for tumor blood vessel growth, cutting off the tumor’s nutrient supply -- preventing disease progression. Dr. Bruce will utilize advanced molecular imaging methods include PET/CT scans to monitor tumor responses in patients treated with TRC105 and assess its overall efficacy.

The Ben Franklin – PCF Young Investigator Award

Robert Den, MD

Kimmel Cancer Center, Thomas Jefferson University – Philadelphia, PA

Radiation therapy in combination with medicines that block testosterone (hormonal therapy) is a common treatment for locally advanced prostate cancer. However, a subset of these patients will not be cured with this treatment and an understanding of the mechanisms of radiation treatment failure is urgently needed. One cause of resistance to radiation treatment might be the loss of a gene called retinoblastoma (RB), which acts in normal tissues to suppress cancer. Dr. Den will investigate the role of RB loss in radiation resistance. He will explore the mechanisms of RB loss during hormonal and radiation therapy in model systems. This work could establish RB as a biomarker for radiation sensitivity and allow physicians to better select patients who have a higher likelihood of being cured by this very common treatment.

The Lynda & Stewart Resnick – PCF Young Investigator Award

David S. Finley, MD

University of California, Los Angeles – Los Angeles, CA

Obesity increases the risk of developing prostate cancer and most major cancers. New data suggests that adipose tissue (body fat), now considered an “organ,” is capable of secreting numerous molecules involved in inflammation and cancer cell proliferation and survival. Fat around organs (e.g. prostate fat) is biologically different than other types of peripheral fat (e.g. abdominal wall). Dr. Finley hypothesizes that fat overlying the prostate may be directly involved in prostate cancer carcinogenesis and that periprostatic fat is a “micro-organ” that may regulate tumor growth and aggressiveness. Dr. Finley previously presented the first data to show that organ-specific fat may promote prostate tumorigenesis. His project will examine a wider array of cancer-associated proteins in the prostate fat and their affect on disease progression.

The Winter Vinecki – PCF Young Investigator Award Sponsored by Lori Milken

Isla Garraway, MD, PhD

University of California, Los Angeles – Los Angeles, CA

A hypothesis for the origin of treatment resistance in prostate cancer is the presence of a small population of cancer stem cells that are capable of regenerating an entire tumor from a single cell. The presence of cancer stem cells theoretically makes cancer incurable if a treatment is not capable of eradicating this very small number of tumor-regenerating cells. Dr. Garraway’s research goal is to define and characterize the origin of human prostate cancer stem cells. This will result in the ability to target better and eradicate these cells that currently evade medical treatments. She is a urologist and her own patients are voluntary donors of samples for human prostate cancer stem cell research.

The William Bikoff – PCF Young Investigator Award

Hans Hammers, MD, PhD

Johns Hopkins University Medical School – Baltimore, MD

Dr. Hammers has initiated a project to determine the mechanisms of resistance of advanced prostate cancer to angiogenesis inhibitors, like Avastin, that block the development of new blood vessels that supply blood and nutrients to developing tumors. Early and impressive results from Dr. Hammers’ work reveals that resistant tumors display a marked increase in pericytes, cells that support small, new, blood vessels. Pericytes are hypothesized to promote angiogenesis in prostate cancer. The goal of this project is to search a large library of compounds that are FDA-approved for the treatment of life threatening diseases but have not been tested against pericytes. Compounds that can inhibit the association of pericytes to blood vessels and therefore impair resistance mechanisms of tumors to angiogenesis inhibitors will be selected for testing. If successful, clinical testing of these compounds can occur expeditiously within the PCF/DoD Therapy Consortium as they are already in clinical use for the treatment of patients with other diseases.

The Charles Dolan-Mark Walter – PCF Young Investigator Award

Daniel Hamstra, MD, PhD

University of Michigan – Ann Arbor, MI

The molecular processes that predict who will have a local recurrence after radiation therapy and who will not are not precisely understood. New evidence suggests that prostate tumors with abnormal blood vessel growth (neo-angiogenesis) are more clinically aggressive and likely to recur. The data also suggests that one prominent cellular survival pathway, the PI3K/Akt/mTOR pathway, plays a vital role in prostate cancer and prostate blood vessel resistance to radiation therapy. Dr. Hamstra’s project is focused on developing new treatment strategies that impair blood vessel proliferation and cell growth, and “sterilize” the fast growing tumor via treating patients with new agents that block the PI3K/Akt/mTOR pathway while radiation therapy is being given.

The Heritage Medical Research Institute– PCF Young Investigator Award

Hannelore Heemers, PhD

Roswell Park Cancer Institute – Buffalo, NY

Androgens (testosterone and related sex hormones) drive the growth and survival of prostate cancer. For almost seven decades, reducing androgens in patients with prostate cancer has been a widely utilized therapy. Unfortunately, many patients eventually become resistant to this treatment and their cancer progresses. Dr. Heemers’ program will investigate the activation and repression of over 50 genes (transcriptome analyses) caused by the action of testosterone and related sex hormones in human prostate cells from patients. These results may be useful to profile and predict patient responses to hormonal therapy and predict patients’ duration of remission.

The Dendreon - PCF Young Investigator Award

Joshua Lang, MD, MS

University of Wisconsin Carbone Comprehensive Cancer Center – Madison, WI

Immunotherapy activates the body’s own immune system to attack tumor cells. Dr. Lang’s research proposal focuses on increasing the power of immunotherapy for the treatment of advanced prostate cancer. Dr. Lang will study specialized prostate cancer vaccines that are designed to turn a patient’s normal immune response against prostate cancer. He will study medications that can alter the pattern of gene expression in patient immune cells which in turn may enhance them to seek out, and destroy prostate cancer cells at metastases. The overall goal is to combine the medicines that change gene expression patterns with other immune system stimulating drugs and antibodies, and deliver better outcomes in advanced disease.

The Brookdale Foundation – PCF Young Investigator Award

Stanley Liauw, MD

University of Chicago – Chicago, IL

Statins are cholesterol-lowering medications used widely to reduce the risk of cardiovascular disease and related death. There is mounting interest in the potential anti-cancer effects of statins if used in new ways. Statin use has been found to improve some cancer outcomes when used alone or in conjunction with traditional cancer therapies. An unbiased analysis of clinical study outcomes of men with various risk categories of prostate cancer treated with radiation therapy at the University of Chicago demonstrated a higher prevalence of disease-free survival for men who were on statins during treatment. This project will test the hypothesis that statins can increase the sensitivity of patients with prostate cancer to the beneficial effects of radiotherapy. Dr. Liauw will review multi-institutional clinical outcomes data to substantiate initial clinical results indicating that statins improve prostate radiotherapy. The project will also conduct laboratory experiments to understand the mechanism of the interaction between statins and radiotherapy at the tumor, cellular, and molecular levels, and their relationship with the lipid metabolism network and hormonal axis. These experiments may identify a new therapeutic regimen for prostate cancer and identify candidate genes for statin-mediated radiosensitization.

The Stewart Rahr – PCF Young Investigator Award

Christopher Maher, PhD

University of Michigan – Ann Arbor, MI

The speed of sequencing the entire DNA content of human prostate cancer has increased by more than 100 times and the cost has been decreased by over 1,000 times in the past five years. The huge amount of data generated in these studies presents challenges when researchers seek to discover the genetic alterations that cause the initiation and progression of cancer. Dr. Maher and colleagues have developed new software bioinformatic tools to extract such data from mass sequencing efforts for prostate cancer. He proposes to sequence more than 100 prostate cancer RNA profiles in an attempt to classify subsets of prostate cancer patients based on unique genetic alterations. This work will set the stage for the discovery of new targeted therapies for different “species” of advanced prostate cancers that need different treatments.

The David Epstein – PCF Young Investigator Award

Neil Martin, MD, MPH

Dana-Farber Cancer Institute and Brigham and Women’s Hospital – Boston, MA

There is increasing promise in the clinic for using targeted treatments for prostate cancer. Because of the specificity of emerging pharmacologic agents, it will be important to identify and treat men who are most likely to respond to these medications. Dr. Martin is currently developing a new diagnostic platform on clinical biopsies. His work is directed at assessing activation of a specific signaling system in prostate cancer cells—the PI3K pathway—with an aim to produce a simple test to identify men most likely to benefit from this new class of targeted medicines. There are several new PI3K pathway drugs entering the clinic in adult oncology in 2010. The overall goal of this work is to further refine individualized treatment strategies for men with advanced prostate cancer.

The David Epstein – PCF Young Investigator Award

Kenneth May, MD, PhD

Dana-Farber Cancer Institute – Boston, MA

Immunotherapy in the form of Provenge (dendritic cell vaccine) and Ipilimumab (monoclonal antibody) are in front of the FDA for approval this year. Both early research efforts were launched by PCF in the late 1990s. Immunotherapy has shown in some advanced prostate cancer patients clear evidence of extending survival. These studies have led to an appreciation for the critical role that the immune system plays in tumor control, as well as the mechanisms of immune evasion utilized by tumors. A more in-depth understanding of the biology behind these therapies is critical to defining which patients might most benefit from immunotherapies. It can also to guide the development of future immunotherapeutic strategies. Dr. May’s research will investigate the NKG2D pathway used by immune cells to kill tumor cells. Numerous types of cancer, including prostate cancers, have been shown to subvert this pathway and hide from immune system attack by shedding recognition molecules from their surface. By better understanding this pathway, it may be possible to design immune-based therapies to counteract such shedding and restore immune activation and tumor destruction.

PCF Young Investigator Award

Nicholas Mitsiades, MD, PhD

Baylor College of Medicine – Houston, TX

Src is a cancer-causing gene (oncogene) that is “switched” on in many adult human cancers including prostate cancer. The Src signaling pathway is activated in many patients whose cancer is resistant to hormonal treatment for advanced prostate cancer. Dasatinib is a drug that inhibits the oncogene Src. In Phase II clinical trials, Dasatinib provided clinical benefit to ~17% of advanced prostate cancer patients. Dr. Mitsiades’ goal is to develop a non-invasive method of identifying which patients will benefit from Dasatinib treatment and which will not. This information would be an invaluable tool for selection of patients who would most likely respond to this medicine. To accomplish this, Dr. Mitsiades is defining a “molecular signature” in prostate cancer cells that is predictive of response to Dasatinib. The response signature will be assessed using tumor cells isolated from a patient’s blood.

The Stewart Rahr – PCF Young Investigator Award

Akash Patnaik, MD, PhD

Beth Israel Deaconess Medical Center, Harvard Medical School – Boston, MA

Obesity has been identified as an important adverse prognostic factor for death due to prostate cancer. Dr. Patnaik will investigate the molecular mechanisms that link obesity to poor outcomes in prostate cancer patients. Hormones such as insulin are increased in obese patients and are known to drive the progression and survival of prostate cancer cells. Recent epidemiological studies have shown that men who are treated with Metformin, a Type II diabetes medication, have a reduced risk of prostate cancer. Since Type II diabetes and obesity are strongly associated, Dr. Patnaik and his team propose to evaluate the capacity of Metformin and related medications to prolong overall survival of patients with advanced prostate cancer. He will determine the molecular mechanism of action of Metformin in prostate cancer and will gain an understanding of the molecular events caused by obesity, which confer poor prostate cancer prognosis. This work will provide rationale for a new metabolic treatment strategy for advanced prostate cancer.

The Stewart Rahr – PCF Young Investigator Award

Philip Saylor, MD

Massachusetts General Hospital Cancer Center – Boston, MA

Hormonal therapy for prostate cancer causes weight gain, adversely alters cholesterol and other blood lipids, and is associated with increased risk for heart attacks and the development of type II diabetes. Dr. Saylor’s research will improve our understanding of how to counteract metabolic changes caused by hormonal therapy. Healthy adults have specialized collections of brown fat which can burn substantial amounts of calories and may be important in avoiding metabolic problems such as diabetes. Overweight and obese men have reduced amounts of brown fat. Dr. Saylor’s research will determine whether hormonal therapy for prostate cancer also causes changes in levels of healthy brown fat. His findings will advance our understanding of the mechanisms that underlie the metabolic changes caused by hormonal therapy and will promote the development of new clinical strategies to prevent these health risks.

The Richard N. Merkin, MD – PCF Young Investigator Award

Jennifer Schutzman, MD, PhD

University of California, San Francisco – San Francisco, CA

Many genes that are critical for proper embryonic development are disregulated in human cancers. For example, Sprouty genes (Spry1 and Spry2) are both critical for neuronal and early prostate gland development and have also been shown to be downregulated in prostate cancer specimens from some men with prostate cancer. Dr. Schutzman is studying the function of Spry1 and Spry2 during prostate development as well as in prostate tumor growth (tumorigenesis). Early data suggests that Sprouty genes are important inhibitors of cellular proliferation and survival pathways critical in prostate cancer initiation and progression. Dr. Schutzman’s work will define how Spry genes function in the development of prostate cancer. Her work may provide essential information necessary to identify new therapeutic targets for the treatment of prostate cancer.

The Lowell Milken – PCF Young Investigator Award

Jay Shendure, MD, PhD

University of Washington – Seattle, WA

Currently, a comprehensive understanding of the genetic events that cause prostate cancer initiation and progression has not been technologically possible. Dr. Shendure has developed a new biotechnology to exhaustively sequence DNA that overcomes many of these technical hurdles. Dr. Shendure’s primary research focus is to develop next generation DNA sequencing technologies for prostate cancer that are rapid, less expensive, and that will provide pathologists and oncologists enhanced resolution of DNA regions that code for protein production. This project has the potential to identify genes and molecular pathways that are important for prostate cancer initiation, progression, and metastasis at a far greater pace.

The Emilio Bassini – PCF Young Investigator Award

Neha Vapiwala, MD

University of Pennsylvania – Philadelphia, PA

Approximately 30% of patients treated for what is believed to be localized, non-metastatic prostate cancer will progress to advanced disease. One challenge is to identify the mechanisms of therapy resistance and to discover biomarkers predictive of a negative clinical outcome. Dr. Vapiwala’s research goal is to develop methods to obtain directed prostate tissue biopsies at the time of fiducial placement (a reference mark inserted for radiation therapy) in prostate cancer patients who will undergo radiation therapy for localized prostate cancer. The biopsies will be analyzed using molecular biology tools to identify prognostic biomarkers of therapy response and/or resistance. The discovery of such biomarkers would be an invaluable tool for early stage clinical testing designed to evaluate novel radiosensitizing agents (compounds that enhance the effect of radiation therapy). Radiosensitizing agents are vital for enhancing the effectiveness of radiation therapy and preventing later disease progression.

The Durden Foundation – PCF Young Investigator Award

Amina Zoubeidi, MSc, PhD

University of British Columbia, Vancouver Prostate Centre – Vancouver, BC

Dr. Zoubeidi’s research is focused on determining the function of a molecule called Heat Shock Protein 27 (Hsp27), which has been implicated as a promoter of tumor cell movement, invasion and metastasis in many cancers including prostate cancer. Hsp27 supports cell survival during stress conditions, such as cancer treatment. Early results from Dr. Zoubeidi’s team suggests that Hsp27 may also induce a cellular structural change in prostate cancer cells that enable the cells to detach from the tumor microenvironment and move to other sites of the body, resulting in lethal metastasis. Dr. Zoubeidi has outlined a comprehensive plan to describe the molecular “blue-print” of protein interactions orchestrated by Hsp27 that drive progression of prostate cancer. An inhibitor of HSP27 is currently undergoing clinical investigation in advanced prostate cancer. Analysis of specimens from these treated patients will further enable her ability to define the benefits of blocking this molecular pathway.

The David & Judy Fleischer – PCF Young Investigator Award

Amado Zurita, MD

The University of Texas M. D. Anderson Cancer Center – Houston, TX

Dr. Zurita’s research goal is to improve the detection of prostate cancer bone metastasis and ultimately to prevent bone metastasis, an event contributing to the lethality of the disease. A clinical challenge is to predict which patients will develop metastatic disease and which will not. Such information would guide clinicians to treat patients with metastatic potential more aggressively. Cadherin-11 is a protein that has been identified as a candidate cell-adhesion molecule required for bone metastasis. Dr. Zurita will evaluate the use of measurement of Cadherin-11 on prostate cancer cells as a predictive marker for bone metastasis. He will also determine whether detection of Cadherin-11 expression levels on circulating tumor cells (cancer cells that have broken away from the tumor and are found in blood) may provide oncologists with a non-invasive assay to predict metastatic potential. A long-term goal is to target Cadherin-11 therapeutically to prevent prostate cancer bone metastasis.


About the Prostate Cancer Foundation

The Prostate Cancer Foundation is the world’s largest philanthropic source of support for prostate cancer research focused on discovering better treatments and a cure for prostate cancer. Founded in 1993, the PCF has raised more than $370 million and provided funding to more than 1,500 research projects at nearly 200 institutions worldwide. The PCF also advocates for greater awareness of prostate cancer and more governmental research funds. PCF advocacy has helped produce a 20-fold increase in government funding for prostate cancer since 1994. More information about prostate cancer and the PCF can be found at www.pcf.org.

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