Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Tissue-Based Biomarkers in Aggressive Variant Prostate Cancer: A Narrative Review

Version 1 : Received: 17 January 2024 / Approved: 17 January 2024 / Online: 17 January 2024 (11:29:27 CET)

A peer-reviewed article of this Preprint also exists.

Kouroukli, O.; Bravou, V.; Giannitsas, K.; Tzelepi, V. Tissue-Based Diagnostic Biomarkers of Aggressive Variant Prostate Cancer: A Narrative Review. Cancers 2024, 16, 805. Kouroukli, O.; Bravou, V.; Giannitsas, K.; Tzelepi, V. Tissue-Based Diagnostic Biomarkers of Aggressive Variant Prostate Cancer: A Narrative Review. Cancers 2024, 16, 805.

Abstract

Prostate cancer (PC) is a common malignancy of elderly men, characterized by great heterogeneity in its clinical course, ranging from an indolent to a highly aggressive disease. The aggressive variant prostate cancer (AVPC) clinically shows an atypical pattern of disease progression, similar to that of small cell PC (SCPC), and also shares the chemo-responsiveness of SCPC. The term AVPC does not describe a specific histologic subtype of PC but rather the group of tumors that, irrespective of morphology, show an aggressive clinical course, dictated by androgen receptor (AR) indifference. AR indifference represents an adaptive response to androgen deprivation therapy (ADT), driven by epithelial plasticity, an inherent ability of tumor cells to adapt to their environment by changing their phenotypic characteristics in a bi-directional way. The molecular profile of AVPC entails combined alterations in tumor suppressor genes retinoblastoma protein 1 (RB1), tumor protein 53 (TP53) and phosphatase and tensin homolog (PTEN). The understanding of the biologic heterogeneity of castration-resistant PC (CRPC) and the need to identify the subset of patients that would potentially benefit from specific therapies necessitate the development of prognostic and predictive biomarkers. This review aims to discuss the possible pathophysiologic mechanisms of AVPC development and the potential use of emerging tissue-based biomarkers in clinical practice.

Keywords

AVPC; biomarkers; NEPC; transdifferentiation; ADT; tumor suppressors; DDR; epigenetic regulation

Subject

Medicine and Pharmacology, Pathology and Pathobiology

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