title: Lessons from tissue compartment-specific analysis of androgen receptor alterations in prostate cancer.
abstract: Androgen receptor (AR) splice variants (AR-Vs) are constitutively active transcription factors that function in the absence of ligand. AR-Vs represent one of several AR re-activation mechanisms utilized by prostate cancer to circumvent first-line androgen deprivation therapy. Second line therapies such as enzalutamide and abiraterone are treatments that re-target components of the androgen/AR axis. However, these second line therapies do not benefit all patients, and patients that do receive initial benefit can develop resistance rapidly. Alterations in components of the androgen/AR axis, including expression of AR-Vs, appear to be linked to primary as well as secondary resistance to second line therapies. However, some key conclusions appear to differ depending on the tissue compartment and measurement platform utilized for analysis. In this review, alterations in AR and the broader AR pathway will be examined in the context of primary prostate cancer tissue, metastatic castration-resistant prostate cancer tissue, circulating tumor cells, and circulating cell-free tumor DNA. Questions regarding the utility of AR-V measurements to provide prognostic information or predict patient responses to AR-targeted therapies will be addressed.
authors.affiliation: Graduate Program in Microbiology, Immunology, and Cancer Biology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Daniel
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA. Electronic address: dehm@umn.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Dehm
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D014408:Biomarkers, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D017354:Point Mutation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism*; D000072417:Protein Domains; D011944:Receptors, Androgen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D008024:Ligands; D011944:Receptors, Androgen; C114750:TCF20 protein, human; D014157:Transcription Factors
keywords: Androgen receptor splice variant; Castration-resistant prostate cancer; Circulating tumor cell; Prostate cancer