Related Experiment Video
Updated: Nov 26, 2025
Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
Published on: October 24, 2019
Diversity in Androgen Receptor Action Among Treatment-naïve Prostate Cancers Is Reflected in Treatment Response
Salma Ben-Salem1, Qiang Hu2, Yang Liu3
1Department of Cancer Biology, Cleveland Clinic, Cleveland, OH, USA.
Background:
Metastatic prostate cancer (CaP) treatments are evolving rapidly but without evidence-based biomarkers to predict responses, and to maximize remissions and survival.
Objective:
To determine the activity of androgen receptor (AR), the target for default first-line systemic treatment, in localized treatment-naïve CaP and its association with clinical risk factors, molecular markers, CaP subtypes, and predictors of treatment response.
Design Setting And Participants:
We examined 452 bona fide AR target genes in clinical-grade expression profiles from 6532 such CaPs collected between 2013 and 2017 by US physicians ordering the Decipher RP test. Results were validated in three independent smaller cohorts (n = 73, 90, and 127) and clinical CaP AR ChIP-Seq data. Association with CaP differentiation and progression was analyzed in independent datasets.
Outcome Measurements And Statistical Analysis:
Unsupervised clustering of CaPs based on AR target gene expression was aligned with clinical variables, differentiation scores, molecular subtypes, and predictors of response to hormonal therapy, radiotherapy, and chemotherapy. AR target gene sets were analyzed via Gene Set Enrichment Analysis for differentiation and treatment resistance, Ingenuity Pathway Analysis for associated biology, and Cistrome for genomic AR binding site (ARBS) composition.
Results And Limitations:
Expression of eight AR target gene subsignatures gave rise to five CaP clusters, which were preferentially associated with CaP molecular subtypes, differentiation, and predictors of treatment response rather than with clinical variables. Subsignatures differed in contribution to CaP progression, luminal/basal differentiation, CaP biology, and ARBS composition. Validation in prospective trials and optimized quantitation are needed for clinical implementation.
Conclusions:
Measurement of AR activity patterns in treatment-naïve CaP may serve as a first branch of an evidence-based decision tree to optimize personalized treatment plans.
Patient Summary:
Treatment options for metastatic prostate cancer are increasing without information needed to choose the right treatment for the right patient. We found variation in the behavior of the target for the default first-line therapy before treatment, which may help optimize treatment plans.
More Related Videos
08:46Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
07:25A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Related Concept Videos
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:31Adrenergic Receptors: ɑ Subtype
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:22Diversity in Cell Signaling Responses
Graded and Abrupt Responses
Some signaling systems generate...