Liquid Biopsy in Prostate Cancer: A Case for Comprehensive Genomic Characterization of Circulating Tumor Cells.

Abstract

Enumeration of circulating tumor cells (CTCs)3 has proven to be a reliable test for monitoring disease progression in metastatic prostate cancer (mPCa) patients. The next logical step would be to perform comprehensive molecular profiling of CTCs that could provide crucial insights for developing rational drug therapies against metastatic cancer cells in general and in CTCs in particular. However, progress in this aspect has been generally slow, largely because the US Food and Drug Administration (FDA)-cleared CellSearch® CTC enumeration platform uses a proprietary fixative that degrades RNA, rendering it unusable for downstream transcriptomic analyses. As reported in this issue of Clinical Chemistry , Markou et al. (1) have overcome this problem by using the CellCollector® (Gilupi) platform to study multiplex gene expression patterns in epithelial cell adhesion molecule-positive (EpCAM) CTCs isolated from high-risk prostate cancer (PCa) patients. In addition to marked interpatient variability in baseline expression of epithelial, epithelial-to-mesenchymal transition (EMT), and stem cell-related genes, the authors also detected a 55% increase in the expression level of EMT-related markers, along with a 41% decrease in the expression of epithelial markers in CTCs after therapy. A comparison of CTC detection rates between the CellCollector and CellSearch/PSA-EPISPOT/Immuno-fluorescence platforms showed that CellCollector was superior for identifying PCa patients with CTCs in their peripheral blood, arguably owing to its ability to identify and isolate a larger pool of EpCAM-positive CTCs. The CellCollector platform is unique, in that it captures CTCs directly from the patient's peripheral blood. The process involves the introduction of an anti-EpCAM antibody-coated functionalized tip into the patient's peripheral vein through a standard IV cannula and leaving it in situ to expose it to the patient's peripheral blood (30 min). During this time, CTCs expressing EpCAM are captured within the antibody-coated hydrogel surface of the tip and retrieved for downstream …