Tissue- and Liquid-Based Biomarkers in Prostate Cancer Precision Medicine

Abstract

Worldwide, prostate cancer (PC) is the second-most-frequently diagnosed male cancer and the fifth-most-common cause of all cancer-related deaths. Suspicion of PC in a patient is largely based upon clinical signs and the use of prostate-specific antigen (PSA) levels. Although PSA levels have been criticised for a lack of specificity, leading to PC over-diagnosis, it is still the most commonly used biomarker in PC management. Unfortunately, PC is extremely heterogeneous, and it can be difficult to stratify patients whose tumours are unlikely to progress from those that are aggressive and require treatment intensification. Although PC-specific biomarker research has previously focused on disease diagnosis, there is an unmet clinical need for novel prognostic, predictive and treatment response biomarkers that can be used to provide a precision medicine approach to PC management. In particular, the identification of biomarkers at the time of screening/diagnosis that can provide an indication of disease aggressiveness is perhaps the greatest current unmet clinical need in PC management. Largely through advances in genomic and proteomic techniques, exciting pre-clinical and clinical research is continuing to identify potential tissue, blood and urine-based PC-specific biomarkers that may in the future supplement or replace current standard practices. In this review, we describe how PC-specific biomarker research is progressing, including the evolution of PSA-based tests and those novel assays that have gained clinical approval. We also describe alternative diagnostic biomarkers to PSA, in addition to biomarkers that can predict PC aggressiveness and biomarkers that can predict response to certain therapies. We believe that novel biomarker research has the potential to make significant improvements to the clinical management of this disease in the near future.

Heterogeneous Expression and Subcellular Localization of Pyruvate Dehydrogenase Complex in Prostate Cancer

“…Frequent alterations in PCa include gene amplification of MYC transcription factor and androgen receptor (AR), the gene deletion of NKX3.1 homeobox, RB1, and PTEN phosphatase, and the gene reorganization of the ETS family of transcription factors ( 8 – 12 ). Currently, the identification of early tumor markers, including metabolic biomarkers, and molecular targets for effective PCa treatment is a research priority ( 13 – 17 ).…”

Detecting disease associated biomarkers by luminescence modulating phages

“…Also, new candidate biomarkers for PCa, such as mRNA and DNA methylation based biomarkers have been suggested. Some of the biomarkers have been suggested to be preferably associated with aggressive clinically significant PCa 18 . Compared to blood samples urine samples are less complex and require less pretreatment before biomarker analysis.…”

“…In patients with grade group 0–3 the serum PSA levels varied between 3.1 and 17.2 ng/mL. Generally, serum PSA-levels less than 4.0 ng/mL are considered normal and clinicians do not prescribe further investigations 18 .…”

Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer

“…The aim of several novel tissue-, blood- and urine-based biomarkers, (including sub forms of PSA, enzymes other than PSA or genetic and epigenetic signatures) is to increase the diagnostic, prognostic, and predictive capability [ 10 , 11 ]. For several reasons, molecular markers are not used in routine pathology, e.g., insufficient evidence, lack of standardization, complexity of the methods and cost of commercially available biomarkers [ 12 ].…”