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Review
. 2021 Jan 19;10(1):193.
doi: 10.3390/cells10010193.

New Prognostic Biomarkers in Metastatic Castration-Resistant Prostate Cancer

Vincenza Conteduca  1 , Alessandra Mosca  2 , Nicole Brighi  1 , Ugo de Giorgi  1 , Pasquale Rescigno  3
Affiliations
Review

New Prognostic Biomarkers in Metastatic Castration-Resistant Prostate Cancer

Vincenza Conteduca et al. Cells. .

Abstract

Prostate cancer is one of the most frequent cancers in men and is a common cause of cancer-related death. Despite significant progress in the diagnosis and treatment of this tumor, patients who relapse after radical treatments inevitably develop metastatic disease. Patient stratification is therefore key in this type of cancer, and there is an urgent need for prognostic biomarkers that can define patients' risk of cancer-related death. In the last 10 years, multiple prognostic factors have been identified and studied. Here, we review the literature available and discuss the most common aberrant genomic pathways in metastatic castration-resistant prostate cancer shown to have a prognostic relevance in this setting.

Keywords: DNA repair defects; PTEN; androgen receptor; prognostic biomarkers; prostate cancer.

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Conflict of interest statement

Vincenza Conteduca has received speaker honoraria or travel support from Astellas, Janssen-Cilag and Sanofi-Aventis, and has received a consulting fee from Bayer. Nicole Brighi has received travel support from Ipsen, Novartis and Pfizer. Ugo De Giorgi has served as consultant/advisory board member for Astellas, Bayer, BMS, Ipsen, Janssen, Merck, Pfizer and Sanofi; has received travel support from BMS, Ipsen, Janssen and Pfizer; and has received research funding from AstraZeneca, Roche and Sanofi (Inst). The other The authors have no conflicts to declare.

Figures

Figure 1
Figure 1
Androgen-dependent signaling through the androgen receptor (AR). After its production in the testes ad the adrenal glands, testosterone (T) is converted by 5α-reductase to dihydrotestosterone (DHT), its active metabolite. Generally, androgens bind to AR, dissociating chaperone proteins, including members of the heat shock protein family (HSP27 and HSP70). Upon homodimerization, ligand-bound AR dimers translocate to the nucleus where they bind to androgen response elements (ARE), acting as transcription factors to downstream targets. AR-directed drugs are illustrated at their points of pathway alteration: Abiraterone disrupts the androgen biosynthesis inhibiting the 17α-hydroxylase/C17,20-lyase (CYP17), an enzime expressed in testicular, prostate, and adrenal tissue; Flutamide, and Bicalutamide, reversibly, and Enzalutamide, Apalutamide, Darolutamide, irreversibly, prevent testosterone binding to the AR, incapacitating its translocation to the nucleus.
Figure 2
Figure 2
Clinical significance of omics-driven approaches applied to tissue and liquid biopsy analysis in prostate cancer research. The analysis of clinical samples (tissue biopsies, plasma, urine) through the use of novel techniques (such as genomics, transcriptomics, epigenomics and proteomics) allows the identification of prognostic and predictive biomarkers and may guide the development of drugs targeting molecular pathways altered in cancer cells. These advances will contribute to improve patients and treatments selection and to guide personalized interventions for the management of prostate cancer.
See this image and copyright information in PMC

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