ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Targeting Androgen Receptor Activation Function-1 with EPI to Overcome Resistance Mechanisms in Castration-Resistant Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.
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Who cites it
80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations.Prostate cancer and prostatic diseases · 2020Pooled it
- Androgen receptor variant-driven prostate cancer II: advances in clinical investigation.Prostate cancer and prostatic diseases · 2020Pooled it
- Developing a Fluorescence-Based High-Throughput Screening Method for Natural Product Fractions to Identify Inhibitors of AR-V7 for Castration-Resistant Prostate Cancer.Pharmaceutics · 2026Article
- Drugging the intrinsically disordered transactivation domain of androgen receptor.Signal transduction and targeted therapy · 2026Article
- Insulin-like growth factor binding protein-3 serves as a biomarker for resistance to enzalutamide in prostate cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Emerging therapies to overcome antiandrogen resistance and beyond in lethal prostate cancer.Journal of the National Cancer Center · 2026Review
- Androgen receptor reactivation in castration-resistant prostate cancer: mechanisms, epigenetic adaptation, and therapeutic vulnerabilities.Frontiers in oncology · 2026Review
- Emerging Therapeutic Approaches to Engage the Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer.Cancers · 2025Review
- Natural Products Targeting the Androgen Receptor Signaling Pathway: Therapeutic Potential and Mechanisms.Current issues in molecular biology · 2025Review
- Ezetimibe Engineered L14-8 Suppresses Advanced Prostate Cancer by Activating PLK1/TP53-SAT1-Induced Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inhibitors of the transactivation domain of androgen receptor as a therapy for prostate cancer.Steroids · 2024Review
- Developmental Therapeutics in Metastatic Prostate Cancer: New Targets and New Strategies.Cancers · 2024Review
- Exercise accelerates recruitment of CD8BMC cancer · 2024Article
- Androgen Receptor-Interacting Proteins in Prostate Cancer Development and Therapy Resistance.The American journal of pathology · 2024Review
- Treatments Targeting the Androgen Receptor and Its Splice Variants in Breast Cancer.International journal of molecular sciences · 2024Review
- Synthesis and Evaluation of Small Molecule Inhibitors of the Androgen Receptor N-Terminal Domain.ACS medicinal chemistry letters · 2023Article
- Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy.Biomedicines · 2023Review
- α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells.Cancers · 2023Article
- A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance.Science advances · 2023Article
- Cheminformatic Analysis and Machine Learning Modeling to Investigate Androgen Receptor Antagonists to Combat Prostate Cancer.ACS omega · 2023Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
purposePersistent androgen receptor (AR) transcriptional activity is clinically evident in castration-resistant prostate cancer (CRPC). Therefore, AR remains as a viable therapeutic target for CRPC. All current hormonal therapies target the C-terminus ligand-binding domain (LBD) of AR. By using EPI to target AR activation function-1 (AF-1), in the N-terminal domain that is essential for AR transactivation, we evaluate the ability of EPI to overcome several clinically relevant AR-related mechanisms of resistance. EXPERIMENTAL
designTo study the effect of EPI on AR transcriptional activity against overexpressed coactivators, such as SRC1-3 and p300, luciferase reporter assays were performed using LNCaP cells. AR-negative COS-1 cells were employed for reporter assays to examine whether the length of polyglutamine tract affects inhibition by EPI. The effect of EPI on constitutively active AR splice variants was studied in LNCaP95 cells, which express AR-V7 variant. To evaluate the effect of EPI on the proliferation of LNCaP95 cells, we performed in vitro BrdUrd incorporation assay and in vivo studies using xenografts in mice.
resultsEPI effectively overcame several molecular alterations underlying aberrant AR activity, including overexpressed coactivators, AR gain-of-function mutations, and constitutively active AR-V7. EPI inhibited AR transcriptional activity regardless of the length of polyglutamine tract. Importantly, EPI significantly inhibited the in vitro and in vivo proliferation of LNCaP95 prostate cancer cells, which are androgen independent and enzalutamide resistant.
conclusionsThese findings support EPI as a promising therapeutic agent to treat CRPC, particularly against tumors driven by constitutively active AR splice variants that are resistant to LBD-targeting drugs. Clin Cancer Res; 22(17); 4466-77. ©2016 AACRSee related commentary by Sharp et al., p. 4280.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.