Novel Quantifiable In Situ Detection of AR-V7 in Metastatic Castration-resistant Prostate Cancer

Case ID:
C14955
Disclosure Date:
8/25/2017
Description:
Unmet Need
About 1 man in 9 will be diagnosed with prostate cancer during his lifetime. When hormonal therapy stops working against prostate cancer, metastatic castrate-resistant prostate cancer (mCRPC) develops. Men affected with CRPC exhibit the spread of cancer to parts of the body beyond the prostate. The cancer is grows and continue to spreads, despite using hormone therapy. As a result, men with this disease require additional treatments such as chemotherapy or targeted therapy to control the growth of the cancer. To identify the development of CRPC, androgen receptor splice variant 7 (AR-V7) can be detected through splice junctions via reverse transcription polymerase chain reaction (RT-PCR) or RNA in situ hybridization (RISH).  RT-PCR uses samples of cancer tissue or liquid biopsies, such as circulating tumor cells (CTCs) or blood samples. Despite the sensitivity and specificity of RT-PCR, AR-V7 quantification is not possible in mCRPC patients who are CTC-negative. CTC-based tests require fresh blood samples to be delivered and processed within 24 hours of collection. Without detectable CTCs, AR-V7 cannot be detected. The second approach, RISH, allows gene expression visualization with spatial and morphological context. RISH methods, however, lack the resolution to distinguish between AR-V7 and AR-V9, another androgen receptor. Thus, there is a need for a reliable method that can detect significant levels of AR-V7 in patients with prostate cancer.
 
 
Technology Overview
The inventors present a novel RISH assay that detects and quantifies the AR-V7 and full-length AR (AR-FL). This technology presents the first example of splice junction visualization in morphologically intact cells. This also is the first time the RISH test can be used for highly specific and quantifiable detection of AR-V7 mRNA in mCRPC patients. In addition, the AR-V7 RISH tests can detect significant levels of AR-V7 in both tissue and CTCs. To cross-validate AR-V7, the inventors also developed an improved AR-V7 immunohistochemistry (IHC) antibody that shows enhanced specificity on testing in both cell lines and clinical specimens.
 
 
Stage of Development
The RISH assay and quantitative analysis of AR-FL/AR-V7 mRNA levels have been completed using biopsies obtained from mRPC patients. 63 patients from the Johns Hopkins University School of Medicine and the Institute of Cancer Research and Royal Marsden NHS Foundation Trust (UK) underwent biopsy procedures to test the efficacy of this technology. Positive detection of AR-V7 was correlated with indicators of high disease burden. In addition, the IHC results indicate a correlation with the RISH results.
 
 
Publications
Crumbaker M, et al. Eur Urol (2017)
Zhu Y, et.al. Eur Urol (2017)
 
 
Patent Information:
Inventors:
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For Information, Contact:
Nakisha Holder
nickki@jhu.edu
410-614-0300
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