ArticleCancer cell international2025
Molecular analysis of androgen receptor splice variant AR-V3 reveals eminent ambiguity regarding activity and clinical utility.
Article in Cancer cell international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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8 authors.
Funding
Abstract
backgroundAndrogen receptor (AR) splice variants (AR-Vs) have emerged as potential resistance mechanisms to AR-targeted agents (ARTAs) in prostate cancer (PC), particularly in the context of castration-resistant disease. Among them, AR-V3 has been frequently detected, yet its biological function remains unclear due to conflicting results from initial studies. This study aimed to comprehensively investigate the molecular structure, activity, and clinical relevance of AR-V3.
methodsWe constructed plasmids encoding two AR-V3 isoforms-one newly identified isoform matching the human reference genome (AR-V3
resultsRNA-seq of AR-FL + AR-V3 vs. AR-FL alone showed no AR-V3-specific gene expression. Structure modeling revealed poor overall prediction confidence, particularly in the N-terminal domain, with no consistent structural features differentiating AR-V3
conclusionsOur data demonstrate that both AR-V3 isoforms are functionally inactive, lacking autonomous nuclear translocation or transcriptional activity. AR-V3 is not a substrate for NMD, and its protein structure remains poorly defined. While associated with worse overall survival, AR-V3 lacks predictive value for ARTA response, underscoring its limited utility as a biomarker. These findings emphasize the need for functional validation before integrating putative biomarkers into clinical practice.
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