Abstract 1990: New diagnostic technology to detect myeloma cells in the blood of multiple myeloma patients
Authors: Jihyun Lee, Hoin Kang, Soee Kim, Ju Bi Lee, Min-Ji Song, Jung Won Kim
Journal: Cancer Research (2025)

Abstract Introduction: Androgen-receptor splice variant 7 (AR-V7) is constitutively activated isoform of AR and has been associated with the resistance towards AR targeting therapies and development into metastatic castration-resistant prostate cancer (mCRPC). Analysis of AR-V7 expression is an important step in prostate cancer diagnosis and determining the therapeutic drug, but the detection of AR-V7 with tissues has limitations such as clinical challenge to poorly accessible tumor tissues before and after treatment. Here, we developed the method of AR-V7 detection in circulating tumor cells (CTC) after isolation with CytoGen’s. Smart Biopsy CTC isolator by droplet digital polymerase chain reaction (ddPCR) with high sensitivity and specificity, overcoming the limitations of tissue biopsy. Method: Sensitivity and specificity were tested using AR-V7 positive cells (VCaP or 22Rv1) and negative cells (PBMC). Limit of detection (LOD) test of AR-V7 expression was performed that AR-V7 positive cells (10 and 5 cells) were spiked into human blood sample (5mL, healthy donor) to mimic CTC after isolation by CytoGen’s Smart Biopsy CTC isolator, subsequently AR-V7 expression was tested with ddPCR. All ddPCR processes included droplet making and reading for each assay were performed on the QX200 ddPCR System (Bio-Rad). For the clinical evaluation, blood samples (each 20mL) of metastatic prostate cancer patients (n=5) were tested with IF assay (5mL) to count CTC number and ddPCR (15ml) to analyze the expression of AR-V7. Results: In in vitro spiking test, AR-V7 expression was clearly detected in the LOD test of AR-V7 positive cells spiked into human blood and was not detected at all in the negative controls. In clinical evaluation study, isolation of CTC from the blood of prostate cancer patients using CytoGen’s Smart Biopsy CTC isolator was confirmed from the result of IF assay, and the expression of AR-V7 in CTC was successfully detected by ddPCR. IF analysis identified 3 or more CTCs in 5 ml of blood from all patients, and expression of AR-V7 was verified by ddPCR in 4 out of 5 mCRPC patients.. These results demonstrate that it is possible to clearly detect the presence of RNA variants is related with drug resistance in mCRPC patients using liquid biopsy, utilizing CTCs, which exist in only very small quantities in the blood. Conclusions: AR-V7 expresses only a part of cancer tissue, so it is difficult to accurately diagnose with traditional histological assays. Detection of AR-V7 (RNA signature) in intact live CTC might overcome limitations of tissue biopsy. In this study, we developed the method to detect AR-V7 in CTC, and presented the results of verifying AR-V7 expression using in vitro models and blood of mCRPC patients. Expanded clinical validation study with more patients’ samples and clinical correlation between AR-V7 expression in CTC and clinical outcome will be performed and analyzed. Citation Format: Jihyun Lee, Hoin Kang, Soee Kim, Ju Bi Lee, Min-Ji Song, Jung Won Kim. New diagnostic technology to detect myeloma cells in the blood of multiple myeloma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1990.