S Wach1, H Taubert2, M Cronauer3. 1. Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nürnberg, Hartmannstrasse 14, 91054, Erlangen, Germany. sven.wach@uk-erlangen.de. 2. Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nürnberg, Hartmannstrasse 14, 91054, Erlangen, Germany. 3. Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
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.
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.
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