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Updated: Mar 21, 2026
Quantitation of Protein Expression and Co-localization Using Multiplexed Immuno-histochemical Staining and Multispectral Imaging
Published on: April 8, 2016
Lessons from tissue compartment-specific analysis of androgen receptor alterations in prostate cancer
1Graduate Program in Microbiology, Immunology, and Cancer Biology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
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.
Insights
Androgen receptor splice variants (AR-Vs) drive prostate cancer treatment resistance. This review examines AR alterations in various cancer tissues and circulating DNA to understand resistance mechanisms and improve therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Androgen receptor (AR) splice variants (AR-Vs) are key drivers of prostate cancer progression.
- AR-Vs enable cancer cells to bypass androgen deprivation therapy (ADT).
- Resistance to second-line therapies like enzalutamide and abiraterone is a major clinical challenge.
Purpose of the Study:
- To review alterations in the AR pathway, including AR-Vs, in prostate cancer.
- To explore the role of AR alterations in primary and acquired resistance to ADT and AR-targeted therapies.
- To address the utility of AR-V measurements for prognosis and predicting treatment response.
Main Methods:
- Literature review of studies analyzing AR and AR-V alterations.
- Examination of data from primary prostate cancer, metastatic castration-resistant prostate cancer (mCRPC), circulating tumor cells (CTCs), and cell-free tumor DNA (cfDNA).
- Analysis of different tissue compartments and measurement platforms.
Main Results:
- AR-Vs are implicated in both primary and secondary resistance to AR-targeted therapies.
- AR pathway alterations are observed across diverse sample types, including primary tumors, mCRPC, CTCs, and cfDNA.
- Discrepancies in findings highlight the importance of tissue compartment and measurement platform.
Conclusions:
- Understanding AR pathway alterations, especially AR-Vs, is crucial for overcoming treatment resistance in prostate cancer.
- AR-V expression may serve as a prognostic biomarker and a predictor of response to AR-targeted agents.
- Further research is needed to standardize AR-V detection and clinical application.
