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Role of androgen receptor splice variants, their clinical relevance and treatment options

  • S. WachEmail author
  • H. Taubert
  • M. Cronauer
Topic Paper
  • 138 Downloads

Abstract

Purpose

In this review, we summarize the importance of AR variants with a particular focus on clinically relevant members of this family.

Methods

A non-systematic literature review was performed based on Medline and PubMed.

Results

Endocrine therapy represents the central paradigm for the management of prostate cancer. Eventually, in response to androgen ablation therapy, several resistance mechanisms against the endocrine therapy might develop that can circumvent the therapy approaches. One specific resistance mechanism that has gained increasing attention is the generation of alternatively spliced variants of the androgen receptor, with AR-V7 being the most prominent. More broadly, AR-V7 is one member of a group of alternatively spliced AR variants that share a common feature, the missing ligand-binding domain. These ΔLBD androgen receptor variants have shown the capability to induce androgen receptor-mediated gene transcription even under conditions of androgen deprivation and to drive cancer progression.

Conclusion

The methods used for detecting AR-Vs, at least on the mRNA level, are well-advanced and harbor the potential to be introduced into clinical diagnostics. It is important to note, that the testing, especially of AR-V7 has its limitations in predicting treatment response. More promising is the great number of active clinical trials aimed at reducing the AR-Vs, and using this to re-sensitize CRPC towards endocrine treatment might provide additional treatment options for CRPC patients in the future.

Keywords

Androgen receptor Splice variant AR-V Clinical relevance 

Notes

Authors’ contribution

SW: manuscript writing and editing. HT: manuscript writing and editing. MC: manuscript writing and editing.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

345_2018_2619_MOESM1_ESM.xlsx (13 kb)
Supplementary material 1 (XLSX 12 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Urology and Pediatric Urology, University Hospital ErlangenFriedrich Alexander-University Erlangen–NürnbergErlangenGermany
  2. 2.Department of UrologyUniversity Hospital Schleswig-HolsteinLübeckGermany

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