Clinical Applications of Molecular Biomarkers in Prostate Cancer

Abstract

There is clinically relevant molecular heterogeneity in prostate cancer (PCa), but this biological diversity has had only a minimal impact on clinical practice. Treatment outcomes in patients with localised PCa are often highly variable, even among patients stratified to the same risk group or disease state based on standard clinical and pathological parameters. In recent years, the development of gene panels has provided valuable data on the differential expression of genes in patients with PCa. Nevertheless, there is an urgent need to identify and validate prognostic and predictive biomarkers that can be applied across clinical scenarios, ranging from localised disease to metastatic castration-resistant PCa. The availability of such tools would allow for precision medicine to finally reach PCa patients. In this review, we evaluate current data on molecular biomarkers for PCa, with an emphasis on the biomarkers and gene panels with the most robust evidence to support their application in routine clinical practice.

Immunotherapy as a Precision Medicine Tool for the Treatment of Prostate Cancer

“…Diagnostic biomarkers for PCa are essentially prostate-specific antigens with the potential to not only discriminate between indolent and advanced disease, but also to be targeted therapeutically; these include prostate-specific-antigen (PSA), prostate acid phosphatase (PAP), prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), prostate cancer antigen 3 (PCA3), NY-ESO-1, mucin-1 (MUC1), GRB2-like endophilin B2 (SH3GLB2), T-cell receptor alternate reading frame protein (TARP) and the six transmembrane epithelial antigens of the prostate (STEAP), among many others [ 40 , 41 ]. During the last decade, there has been a significant increase in the number of identified prostate-specific genomic biomarkers that can be used to reliably estimate relative genetic risk, prognosis and tumor aggressiveness of the disease, and have therefore been the subject of intense investigation for their significance in the decision for therapy selection [ 42 , 43 , 44 , 45 ]. Importantly, PCa biomarkers can also become molecular targets for immunotherapy: diagnostic biomarkers because they constitute prostate-specific antigens that the immune system can be primed to recognize, and genomic biomarkers because they may include genes that are involved in the regulation of the immune response [ 43 ].…”

Diagnostic Strategies for Treatment Selection in Advanced Prostate Cancer

“…There are several biomarkers identified for PCa screening [ 10 , 11 ] ( Table 1 ) with the most ubiquitous and widely adopted being the Prostate-Specific Antigen (PSA), which was approved by the US Food and Drug Administration (FDA) in 1986. PSA screening has had a large impact on trends in PCa incidence and mortality and its widespread adoption has been scrutinized since its discovery 40 years ago [ 12 ].…”

Genetics of Prostate Carcinoma

“…The test results predict a 5-year risk for clinical metastases and 10-year PCa-specific mortality risk from both specimens. It adds to the accuracy for predicting the existence of a high-grade PCa from the biopsy and is also helpful for making decisions related to therapy protocol (radiation therapy timing and hormone deprivation therapy) (14). Prolaris determines RNA expression of 31 cell cycle progression genes and 15 housekeeping genes in biopsy or prostatectomy specimens to predict cancer aggressiveness, PCa-specific mortality, and therapy decision-making (active surveillance or definitive treatment) (15).…”