Liquid Biopsy Based Circulating Biomarkers in Metastatic Prostate Cancer

Abstract

Prostate cancer is the most dominant male malignancy worldwide. The clinical presentation of prostate cancer ranges from localized indolent to rapidly progressing lethal metastatic disease. Despite a decline in death rate over the past years, with the advent of early diagnosis and new treatment options, challenges remain towards the management of metastatic prostate cancer, particularly metastatic castration sensitive prostate cancer (mCSPC) and castration resistant prostate cancer (mCRPC). Current treatments involve a combination of chemotherapy with androgen deprivation therapy and/or androgen receptor signalling inhibitors. However, treatment outcomes are heterogeneous due to significant tumor heterogeneity indicating a need for better prognostic biomarkers to identify patients with poor outcomes. Liquid biopsy has opened a plethora of opportunities from early diagnosis to (personalized) therapeutic disease interventions. In this review, we first provide recent insights about (metastatic) prostate cancer and its current treatment landscape. We highlight recent studies involving various circulating biomarkers such as circulating tumor cells, genetic markers, circulating nucleic acids, extracellular vesicles, tumor-educated platelets, and the secretome from (circulating) tumor cells and tumor microenvironment in metastatic prostate cancer. The comprehensive array of biomarkers can provide a powerful approach to understanding the spectrum of prostate cancer disease and guide in developing improved and personalized treatments for patients.

Biomarkers for the Detection and Risk Stratification of Aggressive Prostate Cancer

“…The WGS analysis of cfDNA revealed multiple mutations and CNAs consistent with PCa tissue analyses: BRCA1/2 , TP53 , SPOP , ATM , APC , and CHEK2 mutations, as well as CNAs in TMPRSS2-ERG and RB1, and PTEN deletions, AR and MYC amplification ( Figure 2 ) [ 55 , 56 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 ]. AR and its constitutively active splice variants, AR-V7 and AR-V3 , are associated with poor survival and are used as potential biomarkers in PCa [ 151 , 152 ].…”

“…An elevated level of IL-8 has been observed in cell lines with invasive behavior, compared to those less likely to progress [ 198 ]. Matrix metallopeptidases (MMPs) are a group of zinc-dependent endopeptidases known as facilitators of tumor invasion and metastasis via degrading connective tissue barriers [ 55 , 199 ]. Analyzing CTC-secreted MMPs revealed higher levels of MMP-2 and MMP-9 expression in aggressive compared to indolent PCa [ 199 , 200 ].…”

“… Common genomic and epigenomic instabilities detected in tissue, blood, and urine of PCa patients [ 17 , 29 , 35 , 39 , 55 , 56 ]. Created with .…”

mFast‐SeqS‐based aneuploidy score in circulating cell‐free DNA is a prognostic biomarker in prostate cancer

“…As previously detailed by Isebia et al [1] and Onstenk et al [17] for the CABA-V7 and CABARESC trials, enrichment and the subsequent enumeration of CTCs were performed similarly. Briefly, blood samples were collected in CellSave Preservative tubes (CS) (Menarini Silicon Biosystems, Bologna, Italy) and processed within 96 h after withdrawal using the CellSearch Ò system (Menarini Silicon Biosystems) according to the manufacturer's instructions.…”

Prognostic significance of lncRNA AP004608.1 in prostate cancer

“…PSA is an organ but not a cancer-specific marker, its sensitivity ranges between 67.5% and 80%, therefore, about 20-30% of could not be diagnosed (3). Liquid biopsy based on circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA) and RNA (ctRNA) has emerged as an attractive and promising strategy complementary to invasive tissue biopsy to guide diagnosis and treatment (3,(17)(18)(19). What's more, liquid biopsy showed a significant potential to modify PCa management since ability to represent comprehensive information and follow-up the progression of PCa.…”