Evaluation of Androgen Receptor Function in Prostate Cancer Prognosis and Therapeutic Stratification
Annual rept. 30 Sep 2013-29 Sep 2014
HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLE MD
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Androgen ablation therapy remains the standard treatment to control advanced prostate cancer. While prostate cancers initially respond to androgen ablation therapy, tumors often become treatment resistant as tumor cells develop mechanisms to evade the treatment. Dysfunction of the androgen receptor frequently observed in castration resistant stages of prostate cancer. We reasoned that early knowledge of androgen receptor dysfunction can predict the course of prostate cancer progression. We proposed an approach for monitoring potential dysfunctions of the androgen receptor by measuring the expression of a panel of genes directly regulated by androgen receptor. We examined human prostate cancer tissues surgery or diagnostic biopsy specimens at early stages of the disease and matched with longitudinal follow up data. We have completed the qRT-PCR evaluation of in 77 patients by monitoring ERG, PSA, PMEPA1 and GAPDH levels. Also, we have completed the evaluation of 80 whole-mounted sections of radical prostatectomy specimens by immunohistochemistry assessing AR, ERG, NKX3.1 and PSA proteins. This study is addressing the association of AR function defects decreased or attenuated expression of ARP genes with unfavorable clinical features, as well as, if expression levels of the androgen regulated gene panel is indicative of biochemical recurrence- and metastasis-free survival. Leveraging the high representation of African American men in the CPDR data and tissue bank we continue to evaluate the performance of the androgen regulated gene panel in both Caucasian American and African American men in response to the emerging need for biomarkers that performs equally well in ethnic groups within the United States.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research