ArticleNature2015
Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 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.
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.
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Who cites it
126 citing papers in PubMed, 252 citations in OpenAlex.
- Baseline serum testosterone and differential efficacy of bipolar androgen therapy and enzalutamide in the randomized TRANSFORMER trial.Prostate cancer and prostatic diseases · 2025Trial
- HSD3B1 Genotype and Clinical Outcomes in Metastatic Castration-Sensitive Prostate Cancer.JAMA oncology · 2020Trial
- Association of Tissue Abiraterone Levels andClinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Testicular vs adrenal sources of hydroxy-androgens in prostate cancer.Endocrine-related cancer · 2017Trial
- SRD5A2 and emerging therapies in androgen-driven disorders.Nature reviews. Urology · 2026Review
- Synthesis of the Abiraterone Derivatives 5α- and 5β-ΔChembiochem : a European journal of chemical biology · 2025Article
- A bypass gateway from cholesterol to sex steroid biosynthesis circumnavigates CYP17A1.Nature communications · 2025Article
- Fine structural design of 3βHSD1 inhibitors for prostate cancer therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HSD3B1, prostate cancer mortality and modifiable outcomes.Nature reviews. Urology · 2025Review
- Luteinizing hormone-releasing hormone receptor agonists and antagonists in prostate cancer: effects on long-term survival and combined therapy with next-generation hormonal agents.Cancer biology & medicine · 2024Review
- Abiraterone and Galeterone, Powerful Tools Against Prostate Cancer: Present and Perspective.Pharmaceutics · 2024Review
- Survival of men with metastatic hormone-sensitive prostate cancer and adrenal-permissive HSD3B1 inheritance.The Journal of clinical investigation · 2024Article
- Identification of novel metabolites of abiraterone in human serum and their metabolic pathways.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2024Article
- Orexins and Prostate Cancer: State of the Art and Potential Experimental and Therapeutic Perspectives.Cancer genomics & proteomics · 2023Review
- Targeting sex steroid biosynthesis for breast and prostate cancer therapy.Nature reviews. Cancer · 2023Review
- Targeting the Androgen Signaling Axis in Prostate Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Review
- Murine toxicology and pharmacokinetics of lead next generation galeterone analog, VNPP433-3β.Steroids · 2023Article
- Pharmacological Efficacy of Repurposing Drugs in the Treatment of Prostate Cancer.International journal of molecular sciences · 2023Review
- The role of 11-oxygenated androgens in prostate cancer.Endocrine oncology (Bristol, England) · 2023Review
- The clinical efficacy and limitations of dutasteride-regulated abiraterone metabolism in abiraterone-resistant patients: a prospective single-arm clinical trial in Chinese patients.Translational andrology and urology · 2022Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Prostate cancer resistance to castration occurs because tumours acquire the metabolic capability of converting precursor steroids to 5α-dihydrotestosterone (DHT), promoting signalling by the androgen receptor and the development of castration-resistant prostate cancer. Essential for resistance, DHT synthesis from adrenal precursor steroids or possibly from de novo synthesis from cholesterol commonly requires enzymatic reactions by 3β-hydroxysteroid dehydrogenase (3βHSD), steroid-5α-reductase (SRD5A) and 17β-hydroxysteroid dehydrogenase (17βHSD) isoenzymes. Abiraterone, a steroidal 17α-hydroxylase/17,20-lyase (CYP17A1) inhibitor, blocks this synthetic process and prolongs survival. We hypothesized that abiraterone is converted by an enzyme to the more active Δ(4)-abiraterone (D4A), which blocks multiple steroidogenic enzymes and antagonizes the androgen receptor, providing an additional explanation for abiraterone's clinical activity. Here we show that abiraterone is converted to D4A in mice and patients with prostate cancer. D4A inhibits CYP17A1, 3βHSD and SRD5A, which are required for DHT synthesis. Furthermore, competitive androgen receptor antagonism by D4A is comparable to the potent antagonist enzalutamide. D4A also has more potent anti-tumour activity against xenograft tumours than abiraterone. Our findings suggest an additional explanation-conversion to a more active agent-for abiraterone's survival extension. We propose that direct treatment with D4A would be more clinically effective than abiraterone treatment.
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What OpenQuestion holds
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.