ArticleThe Journal of clinical investigation2017
Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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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.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- Phase 2 Study of Seviteronel (INO-464) in Patients With Metastatic Castration-Resistant Prostate Cancer After Enzalutamide Treatment.Clinical genitourinary cancer · 2020Trial
- Discovery of BMS-986365, a First-in-Class Dual Androgen Receptor Ligand-Directed Degrader and Antagonist, for the Treatment of Advanced Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Molecular mechanisms and classification of castration-resistant prostate cancer: Insights into androgen receptor, cancer stem cells, and neuroendocrine features.Current urology · 2026Article
- Targeting androgen receptor signaling to enhance cancer immunotherapy.Trends in pharmacological sciences · 2025Review
- Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment.Biomedicines · 2025Review
- Human Cytochrome P450 Cancer-Related Metabolic Activities and Gene Polymorphisms: A Review.Cells · 2024Review
- Abiraterone and Galeterone, Powerful Tools Against Prostate Cancer: Present and Perspective.Pharmaceutics · 2024Review
- The Role of CENPK Splice Variant in Abiraterone Response in Metastatic Castration-Resistant Prostate Cancer.Cells · 2024Article
- Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450.Biomolecules · 2024Article
- Review
- Review
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- wSDTNBI: a novel network-based inference method for virtual screening.Chemical science · 2022Article
- Activity of Combined Androgen Receptor Antagonism and Cell Cycle Inhibition in Androgen Receptor Positive Triple Negative Breast Cancer.Molecular cancer therapeutics · 2021Article
- Steroidogenic cytochrome P450 17A1 structure and function.Molecular and cellular endocrinology · 2021Review
- Steroid Hormone Receptor and Infiltrating Immune Cell Status Reveals Therapeutic Vulnerabilities ofCancer research · 2021Article
- HighFrontiers in oncology · 2021Article
- Expression of the Androgen Receptor Governs Radiation Resistance in a Subset of Glioblastomas Vulnerable to Antiandrogen Therapy.Molecular cancer therapeutics · 2020Article
- Androgen receptor co-regulation in prostate cancer.Asian journal of urology · 2020Review
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
The clinical utility of inhibiting cytochrome P450 17A1 (CYP17), a cytochrome p450 enzyme that is required for the production of androgens, has been exemplified by the approval of abiraterone for the treatment of castration-resistant prostate cancer (CRPC). Recently, however, it has been reported that CYP17 inhibitors can interact directly with the androgen receptor (AR). A phase I study recently reported that seviteronel, a CYP17 lyase-selective inhibitor, ædemonstrated a sustained reduction in prostate-specific antigen in a patient with CRPC, and another study showed seviteronel's direct effects on AR function. This suggested that seviteronel may have therapeutically relevant activities in addition to its ability to inhibit androgen production. Here, we have demonstrated that CYP17 inhibitors, with the exception of orteronel, can function as competitive AR antagonists. Conformational profiling revealed that the CYP17 inhibitor-bound AR adopted a conformation that resembled the unliganded AR (apo-AR), precluding nuclear localization and DNA binding. Further, we observed that seviteronel and abiraterone inhibited the growth of tumor xenografts expressing the clinically relevant mutation AR-F876L and that this activity could be attributed entirely to competitive AR antagonism. The results of this study suggest that the ability of CYP17 inhibitors to directly antagonize the AR may contribute to their clinical efficacy in CRPC.
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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.