Liquid biopsy: ready to guide therapy in advanced prostate cancer?

The identification of molecular markers associated with response to specific therapy is a key step for the implementation of personalized treatment strategies in patients with metastatic prostate cancer (PC). Only in a low proportion of patients, biopsies of metastatic tissue are performed. Circulating tumor cells (CTC), cell free-DNA (cfDNA) and RNA offer the potential for non-invasive characterization of disease and molecular stratification of patients. Furthermore, a "liquid biopsy" approach permits longitudinal assessments, allowing sequential monitoring of response and progression and the potential to alter therapy based on observed molecular changes. In PC, CTC enumeration using the CellSearch© platform correlates with survival. Recent studies on the presence of androgen receptor variants in CTC have shown that the such molecular characterization of CTC provides a potential for identifying patients with resistance to agents that inhibit the androgen signaling axis, such as abiraterone and enzalutamide. New developments in CTC isolation, as well as in-vitro and in-vivo analysis of CTC will further promote the use of CTC as a tool for retrieving molecular information from advanced tumors in order to identify mechanisms of therapy resistance. In addition to CTC, nucleic acids such as RNA and cell free DNA (cfDNA) released by tumor cells into the peripheral blood contains important information on transcriptomic and genomic alterations in the tumors. Initial studies have shown that genomic alterations of the androgen receptor and other genes detected in CTC or cfDNA of patients with castration resistant prostate cancer (CRPC) correlate with treatment outcomes to enzalutamide and abiraterone. Due to recent developments in high throughput analysis techniques, it is likely that CTC, cfDNA and RNA will be an important component of personalized treatment strategies in the future. This article is protected by copyright. All rights reserved.

BJU international. 2016 Jul 19 [Epub ahead of print]

Miriam Hegemann, Arnulf Stenzl, Jens Bedke, Kim Nguyen Chi, Peter Colin Black, Tilman Todenhöfer

Department of Urology, University Hospital, Tuebingen, Germany., Department of Urology, University Hospital, Tuebingen, Germany., Department of Urology, University Hospital, Tuebingen, Germany., Vancouver Prostate Centre, Vancouver, Canada., Vancouver Prostate Centre, Vancouver, Canada., Department of Urology, University Hospital, Tuebingen, Germany.

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