For the population science project, we assembled an interdisciplinary team, co-led by applied (epidemiologist) and basic (telomere biologist) scientists, to verify a novel tissue biomarker for prostate cancer prognosis that we discovered - telomere length variability in prostate cancer cells combined with short telomere length in cancer-associated stromal cells ("telomere biomarker"). In our prospective cohort study, men with this combination had 14-times the risk of prostate cancer death;men without this combination rarely died of their cancer over 15 years. Due to the fact that current prognostic factors inadequately distinguish between aggressive and nonaggressive disease, new prognostic biomarkers that inform beyond the currently used clinico-pathologic factors are needed to enhance treatment and surveillance decision-making. We will address this important unmet clinical need for improved risk stratification for prostate cancer patients. While our prior findings point to the clinical utility of the telomere biomarker, we have completed only the discovery phase. Here, we propose to;1) Demonstrate the validity and reproducibility of an automated "TELl-FISH" method, our FISH-based telomere length measurement tool, using the same prospective cohort study in which we made our discovery. A valid and reproducible high-throughput method for measuring the biomarker is needed for the proposed epidemiologic study on prognosis, and in future epidemiologic studies on eariy detection and active surveillance. 2) Conduct a nested case-control study to verify the association between the telomere biomarker, assessed using automated TELl-FISH, and risk of lethal prostate cancer. 3) Determine optimal outpoints to refine the telomere biomarker for prognosis using both cohorts. 4) Evaluate whether prevalence of the refined telomere biomarker differs across age, race, and other patient characteristics. Differences in biomarker prevalence may inform the racial disparity in disease aggressiveness. We will extensively use the Pathology, Biostatistics, and Administrative Gores. We expect the telomere biomarker will be translated for clinical prognostic utility for prostate cancer in a trial in 5 years.
We expect that the telomere biomarker may identify prostate cancer patients who require enhanced treatment and surveillance, and importantly, patients who may not need intensive additional treatment, and possibly may not require treatment at all. Improved risk stratification allowing for individualized clinical management has the potential to increase the benefit to risk, and reduce healthcare costs for prostate cancer.
|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|
Showing the most recent 10 out of 579 publications