Biologic and clinical significance of androgen receptor variants in castration resistant prostate cancer.

Journal Article (Review)

As prostate cancer (PCa) progresses to the lethal castration resistant and metastatic form, genetic and epigenetic adaptation, clonal selection, and evolution of the tumor microenvironment contribute to the emergence of unique biological characteristics under the selective pressure of external stresses. These stresses include the therapies applied in the clinic or laboratory and the exposures of cancers to hormonal, paracrine, or autocrine stimuli in the context of the tumor micro- and macro-environment. The androgen receptor (AR) is a key gene involved in PCa etiology and oncogenesis, including disease development, progression, response to initial hormonal therapies, and subsequent resistance to hormonal therapies. Alterations in the AR signaling pathway have been observed in certain selection contexts and contribute to the resistance to agents that target hormonal regulation of the AR, including standard androgen deprivation therapy, antiandrogens such as enzalutamide, and androgen synthesis inhibition with abiraterone acetate. One such resistance mechanism is the synthesis of constitutively active AR variants lacking the canonical ligand-binding domain. This review focuses on the etiology, characterization, biological properties, and emerging data contributing to the clinical characteristics of AR variants, and suggests approaches to full-length AR and AR variant biomarker validation, assessment, and systemic targeting in the clinic.

Full Text

Duke Authors

Cited Authors

  • Ware, KE; Garcia-Blanco, MA; Armstrong, AJ; Dehm, SM

Published Date

  • August 2014

Published In

Volume / Issue

  • 21 / 4

Start / End Page

  • T87 - T103

PubMed ID

  • 24859991

Electronic International Standard Serial Number (EISSN)

  • 1479-6821

International Standard Serial Number (ISSN)

  • 1351-0088

Digital Object Identifier (DOI)

  • 10.1530/erc-13-0470

Language

  • eng