The PCF Young Investigator Award-Class of 2010 recipients are:
The 2010 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.
Co-Mentor: David Nanus, MD, Medical Director of the Genitourinary Oncology Program and Chief of the Division of Hematology and Medical Oncology at Weill Cornell Medical College.
Co-Mentor: Mark Rubin, MD, Professor of Pathology and Laboratory Medicine, Director of Translational Research Laboratory Services, and Vice Chairman for Experimental Pathology at Weill Cornell Medical College.
The 2010 PCF Young Investigator 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 U.S. 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.
Mentor: Glenn Liu, MD, Associate Professor of Medicine, Section of Medical Oncology and Hematology, at the University of Wisconsin Carbone Comprehensive Cancer Center.
The 2010 David H. Koch – PCF Young Investigator Award
Brett S. Carver, MD
Memorial Sloan-Kettering Cancer Center – New York, NY
Despite advances in the early detection and management of prostate cancer, hormone-refractory disease remains the second most common cause of male cancer deaths in the United States. Inhibition of the androgen receptor (AR), a key signaling pathway responsible for promoting prostate cancer cell growth, invasion and survival, remains a major target for prostate cancer treatment. Another critical signaling pathway, the PI3K pathway, is frequently activated in primary and metastatic prostate cancer. Activation of the PI3K pathway and molecular alterations promoting AR signaling are associated with the development of hormone refractory disease. A number of novel inhibitors of the PI3K and AR pathways are in early clinical development and are promising therapeutic agents for men with prostate cancer.
Dr. Carver’s research will further define the role of the PI3K pathway in promoting hormone-refractory disease, identify which compounds targeting the PI3K and AR pathways provide maximum therapeutic potential, and identify molecular alterations that predict therapeutic response. Collectively this work will identify which combination of therapeutic agents will provide the greatest survival benefit and for which patients.
Mentor: Charles Sawyers, MD, Professor of Medicine, Chair, Human Oncology and Pathogenesis Program; Marie-Josee and Henry R. Kravis Chair at Memorial Sloan-Kettering Cancer Center.
The 2010 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.
Co-Mentor: Karen Knudsen, PhD, Associate Professor, Departments of Cancer Biology and Urology at the Kimmel Cancer Center, Thomas Jefferson University.
Co-Mentor: Adam Dicker, MD, PhD, Interim Chair and Professor, Radiation Research and Translational Biology, at the Kimmel Cancer Center, Thomas Jefferson University.
The 2010 The Republic of Tea – PCF Young Investigator Award
Felix Feng, MD
University of Michigan – Ann Arbor, MI
Radiation therapy represents one of the primary treatment modalities for localized prostate cancer. However, there is a clear need to better identify which localized prostate cancers are radiation-resistant and to intensify therapy for these malignancies while minimizing side effects. Dr. Feng’s research focuses on two common genetic changes found in prostate cancer, ETS gene fusions and PTEN deletion, and the implications of these alterations on radiation resistance. Dr. Feng and others have found that the presence of either ETS fusions or PTEN deletions affect the ability of prostate cancer cells to repair DNA damage, which is a critical component of radiation response. Dr. Feng now seeks to better understand the mechanisms by which these genetic alterations influence DNA repair, to determine if ETS fusions and/or PTEN deletion can be used as biomarkers of radiation resistance in prostate cancer biopsies, and to investigate whether inhibition of specific DNA repair pathways can be combined with radiation therapy to preferentially kill prostate cancers harboring ETS fusions or PTEN deletion. The long-term goal of this research is to use these genetic alterations to help guide the selection of therapies to improve outcomes for patients with locally advanced prostate cancer.
Mentor: Arul Chinnaiyan, MD, PhD, Howard Hughes Medical Institute Investigator, Director of Pathology Research Informatics, Director of Cancer Bioinformatics, S.P. Hicks Endowed Professor of Pathology, American Cancer Society Research Professor, Professor of Urology, at the University of Michigan.
The 2010 Lynda and 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.
Mentor: Robert Reiter, MD, Professor, Urology, Molecular Biology, Co-Director of the Prostate and Genitourinary Oncology Program, Jonsson Comprehensive Cancer Center, Director of Urologic Research, at the University of California, Los Angeles.
The 2010 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.
Mentor: Owen Witte, MD, Director of the Eli and Edyth Broad Center of Regenerative Medicine and Stem Cell Research, Distinguished Professor of Microbiology, Immunology and Molecular Genetics, President’s Chair in Developmental Immunology, Distinguished Professor of Molecular and Medical Pharmacology, David Geffen School of Medicine, at the University of California, Los Angeles.
The 2010 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 reveal 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.
Mentor: Michael Carducci, MD, Professor of Oncology and Urology, Co-Director Genitourinary Prostate Cancer Program, Co-Director Chemical Therapeutics, at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.
The 2010 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.
Mentor: Kenneth Pienta, MD, Professor, Departments of Internal Medicine and Urology, Associate Dean for Clinical and Translational Research, American Cancer Society Clinical Research Professor, Director, Experimental Therapeutics, Michigan Center for Translational Pathology, Director, Michigan Institute for Clinical and Health Research, at the University of Michigan.
The 2010 Ressler-Gertz Family Foundation – PCF Young Investigator Award
Julia Hayes, MD
Dana-Farber Cancer Institute – Boston, MA
Prostate Specific Antigen (PSA) screening is widely used to assist the early diagnosis of prostate cancer. However, benefits of PSA screening are controversial. Dr. Hayes proposes to develop a model that assesses the effect of PSA screening on overall life expectancy and quality of life, and measures PSA screening cost-effectiveness. To accomplish this, she will use large cohorts of existing data from both the United States and Europe that have detailed records of patients who have undergone PSA screening and those who have not. This research will inform clinical decision making and guide future clinical research and health policy.
Co-Mentor: Philip Kantoff, MD, Chief Clinical Research Officer, Director of the Lank Center of Genitourinary Oncology and Chief of the Division of Solid Tumor Oncology at Dana-Farber Cancer Institute.
Co-Mentor: Michael Barry, MD, Director of the Health Services Research Program and Chief of the General Medicine Unit at Massachusetts General Hospital.
The 2010 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.
Mentor: James Mohler, MD, Professor and Chairman of the Department of Urology and Associate Director and Senior Vice President for Translational Research at Roswell Park Cancer Institute.
The 2010 PCF Young Investigator Award (Anonymous Donor)
Andrew C. Hsieh, MD
University of California, San Francisco – San Francisco, CA
Decades of research have revealed the cascade of signaling events that are in part responsible for the initiation and progression of cancer. These molecular pathways are mediated through complex array of proteins called signaling molecules. The PI3K-AKT-mTOR pathway is one such signaling pathway that has been identified as being critical to prostate cancer progression. However, currently available medicines that can block this pathway, such as Rapamyacin, have shown disappointing results in the treatment of prostate cancer. Dr. Hsieh has discovered that the current medicines targeting the PI3K-AKT-mTOR pathway do not effectively impede the activity of an integral member of the pathway mTOR. Therefore, cancer-causing signaling is not blocked. He has identified a new molecule that is a potent inhibitor of mTOR activity. This award will support preclinical studies of this novel molecule that will accelerate its translation in to the clinic for patients with advanced prostate cancer.
Mentor: Davide Ruggero, PhD, Assistant Professor, School of Medicine, University of California, San Francisco.
The 2010 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.
Mentor: Douglas McNeel, MD, PhD, Associate Professor of Medicine, Section of Hematology/Oncology at the University of Wisconsin Carbone Comprehensive Cancer Center.
The 2010 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.
Co-Mentor: Ralph Weichselbaum, MD, Chairman, Radiation and Cellular Oncology Department, Director, Chicago Tumor Institute, and Director, Ludwig Center for Metastasis Research, University of Chicago.
Co-Mentor: Walter Stadler, MD, Director, Genitourinary Program, Chair, Cancer Research Center’s Clinical Trials Review Committee, and Associate Dean for Clinical Research, University of Chicago.
The 2010 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.
Mentor: Arul Chinnaiyan, MD, PhD, Howard Hughes Medical Institute Investigator, Director of Pathology Research Informatics, Director of Cancer Bioinformatics, S.P. Hicks Endowed Professor of Pathology, American Cancer Society Research Professor, Professor of Urology, at the University of Michigan.
The 2010 Stewart Rahr – PCF Young Investigator Award
Ram S. Mani, PhD
University of Michigan – Ann Arbor, MI
Gene fusions in prostate cancer are early genetic alterations thought to initiate the process of cancer growth. These fusions are defined by the joining of two genes normally found in distinct regions of the genome. Dr. Mani proposes to exploit this finding by identifying molecules that block the cellular machinery responsible for generating gene fusions, thereby preventing prostate cancer initiation or progression. The identification of such molecules would define a new class of anti-cancer medicines that could slow cancer progression and may enhance the efficacy of existing treatments.
Mentor: Arul Chinnaiyan, MD, PhD, Howard Hughes Medical Institute Investigator, Director of Pathology Research Informatics, Director of Cancer Bioinformatics, S.P. Hicks Endowed Professor of Pathology, American Cancer Society Research Professor, Professor of Urology, at the University of Michigan.
The 2010 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.
Mentor: Massimo Loda, MD, Professor of Pathology, Harvard Medical School.
The 2010 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.
Co-Mentor: Glenn Dranoff, MD, Associate Professor, Department of Medicine, Harvard Medical School, Director, Human Gene Transfer Laboratory Core and Co-Leader, Cancer Vaccine Center, Medical Oncology, at the Dana-Farber Cancer Institute.
Co-Mentor: Phil Kantoff, MD, Department of Medicine, Harvard Medical School and Director, Lank Center for Genitourinary Oncology, at the Dana-Farber Cancer Institute.
The 2010 Alan G. Hassenfeld – 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.
Mentor: Bert W. O’Malley, MD, Professor and Chair, Department of Molecular and Cellular Biology, Baylor College of Medicine.
The 2010 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.
Mentor: Lewis Cantley, PhD, William Bosworth Castle Professor of Medicine, Professor of Systems Biology at Harvard Medical School, Director of the Cancer Center and the Chief of the Division of Signal Transduction at Beth Israel Deaconess Medical Center.
The 2010 Stewart Rahr – PCF Young Investigator Award
Edwin Posadas, MD
Cedars-Sinai Medical Center – Los Angeles, CA
Dr. Posadas’ research goal is to identify the molecular mechanisms of prostate cancer metastasis. A protein called FYN, which is a member of a cancer-causing gene family, was identified in his laboratory as a possible regulator of metastasis. The biology of metastasis is driven by molecular changes within cancer cells that enable cell motility, which contributes to the spread of cancer throughout the body. Analysis of prostate cancer tumor specimens showed that there were higher levels of FYN in cancer cells as compared to normal cells. Dr. Posadas will comprehensively define the function of FYN in prostate cancer cells. These studies may lead to the development of novel targeted therapies that block FYN function and prevent prostate cancer metastasis and cases of advanced prostate cancer in patients.
Co-Mentor: Walter Stadler, MD, Fred C. Buffett Professor, Departments of Medicine and Surgery, Director, Genitourinary Oncology and Associate Dean of Clinical Research at the University of Chicago.
Co-Mentor: Carrie Rinker-Schaeffer, PhD, Associate Professor for Surgery, Medicine and Obstetrics and Gynecology, Director of Urological Research, the University of Chicago
Co-Mentor: Ravi Salgia, MD, PhD, Professor of Medicine, Director of Thoracic Oncolgoy Research Program and Aerodigestive Tract Program Translational Research Laboratories at the University of Chicago.
The 2010 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.
Mentor: Matthew Smith, MD, PhD, Associate Professor of Medicine, Director of Genitourinary Oncology at Harvard Medical School and Associate Physician, Massachusetts General Hospital.
The 2010 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.
Mentor: Gail Martin, PhD, Professor in the Department of Anatomy at the University of California, San Francisco.
The 2010 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.
Mentor: Peter Nelson, MD, Co-Head, Program in Prostate Cancer Research, Member, Division of Human Biology, Fred Hutchinson Cancer Research Center, and Professor, Departments of Medicine, Pathology and Genome Sciences at the University of Washington.
The 2010 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.
Mentor: Alan Wein, MD, PhD, Professor and Chair of the Division of Urology, University of Pennsylvania School of Medicine and Chief of Urology at the Hospital of the University of Pennsylvania.
The 2010 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.
Mentor: Martin Gleave, MD, Liber Ero British Columbia Leadership Chair in Prostate Cancer Research, Distinguished Professor in the Department of Urologic Sciences at the University of British Columbia and Director, The Vancouver Prostate Centre.
The 2010 David and Judy Fleischer – PCF Young Investigator Award
Amado Zurita, MD
The University of Texas MD 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.
Mentor: Sue-Hwa Lin, PhD, Professor and Deputy Chair, Molecular Pathology, Professor in Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center.