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

Abstract

The identification of molecular markers associated with response to specific therapy is a key step for the implementation of personalised treatment strategies in patients with metastatic prostate cancer. Only in a low proportion of patients biopsies of metastatic tissue are performed. Circulating tumour cells (CTC), cell-free DNA (cfDNA) and RNA offer the potential for non-invasive characterisation 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 prostate cancer, CTC enumeration using the CellSearch© platform correlates with survival. Recent studies on the presence of androgen receptor (AR) variants in CTC have shown that such molecular characterisation of CTC provides a potential for identifying patients with resistance to agents that inhibit the androgen signalling 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 tumours in order to identify mechanisms of therapy resistance. In addition to CTC, nucleic acids such as RNA and cfDNA released by tumour cells into the peripheral blood contain important information on transcriptomic and genomic alterations in the tumours. Initial studies have shown that genomic alterations of the AR and other genes detected in CTC or cfDNA of patients with castration-resistant prostate cancer 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 personalised treatment strategies in the future.

Liquid biopsy: a step forward towards precision medicine in urologic malignancies

“…The Food and Drug Administration (FDA) has approved the CELLSEARCH ® CTC Test for monitoring of patients with metastatic prostate cancer. This test counts CTCs of epithelial origin ( CD45 -, EPCAM +, and cytokeratins 8, 18+, and/or 19+) in whole blood [43]. CTC counts can serve as an estimate for disease burden, and changes in CTC counts over the course of systemic therapy can be indicative of treatment response [44].…”

Prostate Cancer Stem Cell Markers Drive Progression, Therapeutic Resistance, and Bone Metastasis

“…Due to the difficulty of obtaining metastatic or recurrent biopsies, multiple studies have focused on the ability to isolate and quantify CSCs in a “liquid biopsy” using the whole blood of patients. This test would be less invasive and could provide more prognostic information [26, 27]. CSCs enriched from patient whole blood would be representative of a CTC subpopulation but may still miss the CSCs developing in the metastatic niche or after therapy.…”

Cancer-Devoted Liquid Biopsies and Applications to Prostate Cancer

“…Hegemann et al [32]* asked whether liquid biopsy is ready to guide therapy in advanced PCa. They compared CTCs, ctDNAs and circulating RNAs for liquid biopsies of advanced PCa.…”