Journal
CANCERS
Volume 12, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/cancers12082247
Keywords
CTCs; prostate cancer; AR-V7; in situ padlock probe; ARamplification; liquid biopsy; multi-analyte
Categories
Funding
- Federal Ministry of Transport, Innovation and Technology (BMVIT)
- Federal Ministry of Science, Research and Economy (BMWFW)
- Land Steiermark (Department 12, Business and Innovation)
- Styrian Business Promotion Agency (SFG)
- Vienna Business Agency
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Novel androgen receptor (AR) signaling inhibitors have improved the treatment of castration-resistant prostate cancer (CRPC). Nonetheless, the effect of these drugs is often time-limited and eventually most patients become resistant due to various AR alterations. Although liquid biopsy approaches are powerful tools for early detection of such therapy resistances, most assays investigate only a single resistance mechanism. In combination with the typically low abundance of circulating biomarkers, liquid biopsy assays are therefore informative only in a subset of patients. In this pilot study, we aimed to increase overall sensitivity for tumor-related information by combining three liquid biopsy approaches into a multi-analyte approach. In a cohort of 19 CRPC patients, we (1) enumerated and characterized circulating tumor cells (CTCs) by mRNA-based in situ padlock probe analysis, (2) used RT-qPCR to detect cancer-associated transcripts (e.g.,ARandAR-splice variant 7) in lysed whole blood, and (3) conducted shallow whole-genome plasma sequencing to detectARamplification. Although 44-53% of patient samples were informative for each assay, a combination of all three approaches led to improved diagnostic sensitivity, providing tumor-related information in 89% of patients. Additionally, distinct resistance mechanisms co-occurred in two patients, further reinforcing the implementation of multi-analyte liquid biopsy approaches.
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