Posted February 7, 2013
Bruce J. Trock, PhD, Johns Hopkins University
Jonathan Melamed, MD, New York University
The Prostate Cancer Biorepository Network (PCBN), supported by the Department of Defense (DoD) Prostate Cancer Research Program (PCRP), is working toward meeting a critical need in prostate cancer research - the need for human tissues and other biospecimens.
To reduce or eliminate the impact of prostate cancer, researchers need a better understanding of the disease so that new approaches to preventing or treating it can be achieved. Advancements in understanding the disease occur primarily through discoveries made at the basic science, translational, and clinical levels. To bring to patients these discoveries, such as identification of a novel biomarker for detection or diagnosis, a critical component is to determine the relevance of the findings by studying them in human tissues. Unfortunately, there is currently a major roadblock to this in that many researchers do not have access to prostate cancer patient populations and high-quality human tissues, limiting their ability to translate their discoveries into improvements for patients. This critical need for providing high-quality prostate cancer biospecimens to the research community was a focus of discussion during the Fiscal Year 2009 DoD PCRP Vision Setting meeting, and led to a new award mechanism that would support a pilot effort to begin addressing this need. Thus, the Prostate Cancer Pathology Resource Network Award was openly competed and ultimately awarded in June 2010 to the Johns Hopkins University (JHU) and the New York University (NYU) Schools of Medicine for a total investment of approximately $3.2 million, and the PCBN was initiated.
Johns Hopkins University entered into the collaboration with the dual role of being both a Pathology Resource Network Site, with the task of contributing specimens, and the Coordinating Center, led by Dr. Bruce Trock. With the combined efforts of investigators at the NYU site (Dr. Jonathan Melamed, Principal Investigator, and Dr. Peng Lee) and other prominent pathologists at JHU (Drs. Angelo De Marzo and George Netto), the PCBN has utilized PCRP support to facilitate the development of a biorepository whose goal is to facilitate the collection, processing, storage, and distribution of high-quality, well-annotated prostate cancer biospecimens. To date, the specimens available in the PCBN include tissues from prostatectomies (formalin-fixed, paraffin-embedded and fresh-frozen), tissue microarrays (TMAs), body fluids (serum, plasma, buffy coat, prostatic fluid), and derived specimens such asDNA and RNA. Importantly, a large subset of the specimens in the PCBN are also linked to clinical, pathological, and outcome data, and are supported by an informatics infrastructure with the capability to deposit data into currently available systems at the respective institutions. In addition, the PCBN actively investigates improved methods for obtaining, processing, and derivatizing biospecimens, and the impact of such methods on biomarker research. The PCBN website (http://prostatebiorepository.org) provides additional information regarding access to samples for the research community.
Both the DoD PCRP and the PCBN work with additional subject matter experts, including patient advocates, who help to provide critical input for the overall direction of the PCBN. These efforts have helped to produce specific policies and procedures for requesting biospecimens, including review criteria for applications, collaboration requirements for certain types of specimens, and the preservation of confidentiality and intellectual property. The PCBN investigators continually reach out to scientists at national scientific meetings and other venues in an effort to publicize the availability of this valuable resource. One such focused effort is a workshop being held on February 13, 2013 for biorepository experts and leaders in prostate cancer research to come together to discuss topics that will facilitate the use of PCBN biospecimens in the most important areas of prostate cancer research, such as understanding and preventing metastatic disease.
Over 400 samples including TMAs (including those for race-disparity or metastasis studies), DNA, RNA, protein, serum samples, and paraffin sections have been delivered thus far to the scientific community and are producing results that are being published in peer-review journals. In one particular study, PCBN samples enabled urologists at Johns Hopkins to discover that reduction of a specific protein is correlated with the aggressiveness of the disease, acting as a red flag to indicate an increased risk of cancer recurrence. Their study, reported in the Proceedings of the National Academy of Sciences on Aug. 27, 2012, focused on a gene called SPARCL1, which appears to be critically important for cell migration during prostate development in the embryo and becomes active again during cancer progression1. Their findings should allow physicians to not only pinpoint those patients whose cancers are destined to return after surgery, but could also reveal potential new options for treatment.
It is the hope of the DoD PCRP and the PCBN investigators that this resource will continue to gain in utility for the prostate cancer research community, and will continue to enable discoveries toward achieving the PCRP vision of conquering prostate cancer.
1. Hurley, PJ et al. Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome. PNAS Sept, 109(37):14977-14982.