ArticleeLife2013
Overcoming mutation-based resistance to antiandrogens with rational drug design.
Article in eLife, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
201 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Preclinical Anticipation of On- and Off-Target Resistance Mechanisms to Anti-Cancer Drugs: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Development and prevalence of castration-resistant prostate cancer subtypes.Neoplasia (New York, N.Y.) · 2020Pooled it
- A Phase 1/2 multicenter trial of DKN-01 as monotherapy or in combination with docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC).Prostate cancer and prostatic diseases · 2025Trial
- Phase 2 Study of Seviteronel (INO-464) in Patients With Metastatic Castration-Resistant Prostate Cancer After Enzalutamide Treatment.Clinical genitourinary cancer · 2020Trial
- Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- Circulating Tumor DNA as Emerging Predictive and Prognostic Biomarker in Prostate Cancer.Cancers · 2026Review
- High-resolution functional mapping of androgen receptor variants.Nature biomedical engineering · 2026Article
- Androgen Receptor Point Mutations: A Mechanism of Therapeutic Resistance and a Framework for Rational Drug Design.Cancers · 2026Review
- Outcomes for Patients With SPOP Mutated Castration-Resistant Prostate Cancer (CRPC) Treated With an Androgen Receptor Pathway Inhibitor (ARPI).Clinical genitourinary cancer · 2026Article
- ZDHHC2-Dependent Palmitoylation Dictates Ferroptosis and Castration Sensitivity in Prostate Cancer via Controlling ACSL4 Degradation and Lipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rho Small GTPase Family in Androgen-Regulated Prostate Cancer Progression and Metastasis.Cancers · 2025Review
- Elevated VRK1 levels after androgen deprivation therapy promote prostate cancer progression by upregulating YAP1 expression.Journal of cancer research and clinical oncology · 2025Article
- Increased nuclear factor I-mediated chromatin access drives transition to androgen receptor splice variant dependence in prostate cancer.Cell reports · 2025Article
- Small-molecule disruption of androgen receptor-dependent chromatin clusters.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Review
- Article
- Insight into Recent Advances in Degrading Androgen Receptor for Castration-Resistant Prostate Cancer.Cancers · 2024Review
- UBE2J1 is the E2 ubiquitin-conjugating enzyme regulating androgen receptor degradation and antiandrogen resistance.Oncogene · 2024Article
141 more citing papers are in PubMed but not listed here.
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10 authors.
Funding
Abstract
The second-generation antiandrogen enzalutamide was recently approved for patients with castration-resistant prostate cancer. Despite its success, the duration of response is often limited. For previous antiandrogens, one mechanism of resistance is mutation of the androgen receptor (AR). To prospectively identify AR mutations that might confer resistance to enzalutamide, we performed a reporter-based mutagenesis screen and identified a novel mutation, F876L, which converted enzalutamide into an AR agonist. Ectopic expression of AR F876L rescued the growth inhibition of enzalutamide treatment. Molecular dynamics simulations performed on antiandrogen-AR complexes suggested a mechanism by which the F876L substitution alleviates antagonism through repositioning of the coactivator recruiting helix 12. This model then provided the rationale for a focused chemical screen which, based on existing antiandrogen scaffolds, identified three novel compounds that effectively antagonized AR F876L (and AR WT) to suppress the growth of prostate cancer cells resistant to enzalutamide. DOI:http://dx.doi.org/10.7554/eLife.00499.001.
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Registered trials
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.