Abstract 3161: Development and implementation of a non-invasive NGS-based diagnostic test for precision medicine in prostate cancer

Abstract

Abstract The growth and survival of prostate cancer tumors relies primarily on the functioning of the androgen receptor (AR) signaling pathway. Recent studies suggested that the presence of AR-V7, a c-terminal truncated form of AR, in circulating tumor cells (CTCs) of patients with castration-resistant prostate cancer (CRPC) is associated with inherent and/or acquired resistance to enzalutamide and abiraterone, the stand of care androgen deprivation therapies in prostate cancer. A series of data also indicate that AR-Vs (eg, including AR-V7, ARv567es, AR-T878A, AR-F876L, and Arv567es) may drive resistance in CRPC. Expression of AR-Vs has been shown to correlate with disease progression and shortened survival and AR-V7 is most abundant in CRPC specimens. Considering that truncated ARs with C-terminal loss (splice variants) lack a functional LBD and are constitutively active, C-terminal AR-directed therapies may not be effective, and novels agents are needed that target mutated ARs including AR-Vs. Circulating tumor cell (CTC)-based AR-V7 tests are currently being tested in the clinic. However, nearly half of the CRPC patients do not have enough CTCs for AR-V7 test, raising the request for a complementary, non-CTC platform to detect AR variants as well as other resistance markers in circulation. Here we report the successful development of a non-invasive, next generation sequencing-based diagnostics platform that offers comprehensive profiling of genomic alterations in prostate cancer, including splicing variants (such as AR-V7), point mutation, copy number, and translocation using biofluid samples (blood and urine) from CRPC patients. To the best of our knowledge, this is the first non-invasive diagnostic test that measures genetic alterations especially AR-V7 in all patients with prostate cancer, regardless of their status of CTC enumeration. The successful development and clinical validation of this test has potential to enable precision medicine in prostate cancer. Citation Format: Pan Du, Amy Wang, Tak Cheng, Winston Patrick Kuo. Development and implementation of a non-invasive NGS-based diagnostic test for precision medicine in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3161.