The goal of this proposal is to develop a platform technology for detection and therapy of prostate cancer (PCa) based on induced cancer-specific expression of target proteins. In the US active surveillance is being reconsidered as an option for local disease due to the increasing recognition that many men undergo unnecessary prostatectomies. The idea behind active surveillance is that there is an indolent form of PCa that will never metastasize and will therefore not pose a major threat to the patient. There is no way to differentiate indolent from aggressive disease - no marker or panel of markers, no imaging agent to follow the course of the disease in vivo reliably. One approach is that, since it is nearly impossible to determine which tumors will progress, they should all be treated, and preferably when they are small, before they further de-differentiate and begin to metastasize. But they should not all be treated surgically, due to the well-known co-morbidities for resection of PCa, even with modern, nerve-sparing techniques. Recently the US Preventive Services Task Force issued a draft recommendation statement against prostate-specific antigen (PSA) screening for all age groups. The recommendation states that "PSA-based screening results in small or no reduction in PCa-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary." That underscores the need for new, sensitive biomarkers for PCa, which can be used along with PSA history to provide suitable, tailored therapy. We propose a radical new method for detecting and treating PCa, whether it is localized, just beyond the capsule or widespread and metastatic to bone. The method relies on the discovery of a gene promoter, known as the progression elevated gene-3 (PEG-Prom), which is up-regulated in cancer and only cancer, i.e., it remains quiescent within normal or even immortalized normal tissue. When cloned in front of an imaging reporter or a therapeutic gene, these latter genes become activated only in the presence of malignancy - including PCa. We will deliver PEG-Prom systemically in a non-viral vector to relevant experimental models of PCa to delineate and concurrently eradicate it, specifically.

Public Health Relevance

Compared to other cancers, prostate cancer is notoriously difficult to image. It is also impossible to know which tumors will be indolent or which will be aggressive and metastasize, necessitating treatment of all lesions detected - if such treatment is not harmful. By specifically activating imaging reporter and therapeutic genes within prostate cancer, we will be able to detect and treat it safely, irrespective of location.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Special Emphasis Panel (ZCA1-RPRB-7 (M1))
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Johns Hopkins University
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Ku, ShengYu; Lasorsa, Elena; Adelaiye, Remi et al. (2014) Inhibition of Hsp90 augments docetaxel therapy in castrate resistant prostate cancer. PLoS One 9:e103680
Regter, Sietze; Hedayati, Mohammad; Zhang, Yonggang et al. (2014) Androgen withdrawal fails to induce detectable tissue hypoxia in the rat prostate. Prostate 74:805-10
Chalfin, Heather J; Frank, Steven M; Feng, Zhaoyong et al. (2014) Allogeneic versus autologous blood transfusion and survival after radical prostatectomy. Transfusion 54:2168-74
Bhatnagar, Akrita; Wang, Yuchuan; Mease, Ronnie C et al. (2014) AEG-1 promoter-mediated imaging of prostate cancer. Cancer Res 74:5772-81
Brennen, W Nathaniel; Rosen, D Marc; Chaux, Alcides et al. (2014) Pharmacokinetics and toxicology of a fibroblast activation protein (FAP)-activated prodrug in murine xenograft models of human cancer. Prostate 74:1308-19
Paller, C J; Olatoye, D; Xie, S et al. (2014) The effect of the frequency and duration of PSA measurement on PSA doubling time calculations in men with biochemically recurrent prostate cancer. Prostate Cancer Prostatic Dis 17:28-33
Durham, Nicholas M; Nirschl, Christopher J; Jackson, Christopher M et al. (2014) Lymphocyte Activation Gene 3 (LAG-3) modulates the ability of CD4 T-cells to be suppressed in vivo. PLoS One 9:e109080
Gurel, Bora; Lucia, M Scott; Thompson Jr, Ian M et al. (2014) Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev 23:847-56
Lutz, Eric R; Wu, Annie A; Bigelow, Elaine et al. (2014) Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol Res 2:616-31
Zheng, Qizhi; Peskoe, Sarah B; Ribas, Judit et al. (2014) Investigation of miR-21, miR-141, and miR-221 expression levels in prostate adenocarcinoma for associated risk of recurrence after radical prostatectomy. Prostate 74:1655-62

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