Current status of liquid biopsies for the detection and management of prostate cancer

Abstract

In recent years, new therapeutic options have become available for prostate cancer (PC) patients, generating an urgent need for better biomarkers to guide the choice of therapy and monitor treatment response. Liquid biopsies, including circulating tumor cells (CTCs), circulating nucleic acids, and exosomes, have been developed as minimally invasive assays allowing oncologists to monitor PC patients with real-time cellular or molecular information. While CTC counts remain the most extensively validated prognostic biomarker to monitor treatment response, recent advances demonstrate that CTC morphology and androgen receptor characterization can provide additional information to guide the choice of treatment. Characterization of cell-free DNA (cfDNA) is another rapidly emerging field with novel technologies capable of monitoring the evolution of treatment relevant alterations such as those in DNA damage repair genes for poly (ADP-ribose) polymerase (PARP) inhibition. In addition, several new liquid biopsy fields are emerging, including the characterization of heterogeneity, CTC RNA sequencing, the culture and xenografting of CTCs, and the characterization of extracellular vesicles (EVs) and circulating microRNAs. This review describes the clinical utilization of liquid biopsies in the management of PC patients and emerging liquid biopsy technologies with the potential to advance personalized cancer therapy.

Keywords: biomarker; circulating tumor DNA; circulating tumor cell; prostate cancer.

Figure 1

Schematic overview of liquid biopsy analytes and profiling options in prostate cancer. Abbreviations: CTC, circulating tumor cell; EV, extracellular vesicle.

Figure 2

Seminal liquid biopsy studies in prostate cancer. Abbreviations: CTC, circulating tumor cell; cfDNA, cell-free DNA; PC, prostate cancer; mCRPC, metastatic castration resistant prostate cancer; AR, androgen receptor; AR-V7, androgen receptor splice variant-7; ARSI, androgen receptor signaling inhibitor; PARP, poly (adenosine diphosphate [ADP]-ribose) polymerase.

Figure 3

CTC enrichment and detection strategies. CTCs are enriched from whole blood based on biological or physical properties or can be detected directly with high-content imaging. Immunoaffinity-based CTC enrichment is achieved via positive or negative selection for tumor or leukocyte-specific antigens, respectively. Capture efficiency can be enhanced by specifically engineered surfaces that maximize interaction in the microfluidic devices. Physical property-based enrichment exploits differential size, deformability, and dielectric properties to separate CTCs from background leukocytes. The direct analysis employs rapid, high content scanning of all blood cells after fixation in monolayer onto a slide. CTC candidates are identified using automated algorithms based on a combination of morphometric features and immunofluorescent staining for epithelial markers. Abbreviation: CTC, circulating tumor cell.