Blood-based liquid biopsies for prostate cancer: clinical opportunities and challenges

Abstract

Liquid biopsy has been established as a powerful, minimally invasive, tool to detect clinically actionable aberrations across numerous cancer types in real-time. With the development of new therapeutic agents in prostate cancer (PC) including DNA repair targeted therapies, this is especially attractive. However, there is unclarity on how best to screen for PC, improve risk stratification and ultimately how to treat advanced disease. Therefore, there is an urgent need to develop better biomarkers to help guide oncologists’ decisions in these settings. Circulating tumour cells (CTCs), exosomes and cell-free DNA/RNA (cfDNA/cfRNA) analysis, including epigenetic features such as methylation, have all shown potential in prognostication, treatment response assessment and detection of emerging mechanisms of resistance. However, there are still challenges to overcome prior to implementing liquid biopsies in routine clinical practice such as preanalytical considerations including blood collection and storage, the cost of CTC isolation and enrichment, low-circulating tumour content as a limitation for genomic analysis and how to better interpret the sequencing data generated. In this review, we describe an overview of the up-to-date clinical opportunities in the management of PC through blood-based liquid biopsies and the next steps for its implementation in personalised treatment guidance.

Tailored point-of-care biosensors for liquid biopsy in the field of oncology

“…This capability has made liquid biopsy one of the most promising areas of cancer research. 104 The development of POC diagnostics is a direct result of significant technological advances in the field of biosensing. These diagnostics are designed to make the testing process more advisable, user-friendly, and affordable, while allowing measurements to be taken in the field.…”

Molecular Genetics of Prostate Cancer and Role of Genomic Testing

“…22 Finally, recent studies have been assessing the role of liquid biopsy for molecular subtyping and identification of predictive biomarkers in advanced PCa. 62,63,73 Surgical pathologists play a critical role in triaging tissue for molecular biomarker testing in PCa. It is important for pathologists to understand when biomarker testing may be appropriate, and how these tests are performed.…”

Molecular testing of DNA damage response pathways in prostate cancer patients

“…The advantages of NGS includes greater sensitivity from assaying multiple microsatellites in parallel, identifying the mutations responsible for dMMR, and resolving whether genetic variants are somatic or germline [36]. For patients with difficult to biopsy prostate cancer bone metastases, recently developed NGS assays of circulating cell free DNA (cfDNA) are a promising option [37 ▪ ].…”