ArticleCell2013
A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer.
Article in Cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 205 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase IIa Clinical Trial to Evaluate Pharmacokinetics and Safety of Slow Release DHEA
A Study to Evaluate Efficacy and Safety of Slow Release DHEA
Who cites it
205 citing papers in PubMed, 1 synthesis or guideline pooled it, 311 citations in OpenAlex.
- HSD3B1 variant and androgen-deprivation therapy outcome in prostate cancer.Cancer chemotherapy and pharmacology · 2021Pooled it
- HSD3B1 genotype and outcomes in metastatic hormone-sensitive prostate cancer with androgen deprivation therapy and enzalutamide: ARCHES.Cell reports. Medicine · 2024Trial
- Circulating and Intratumoral Adrenal Androgens Correlate with Response to Abiraterone in Men with Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Loss ofJCO precision oncology · 2021Trial
- HSD3B1 Genotype and Clinical Outcomes in Metastatic Castration-Sensitive Prostate Cancer.JAMA oncology · 2020Trial
- Trial
- 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
- 3beta-HSD1-mediated steroid back-conversion maintains androgen signaling in prostate cancer.Molecular cancer research : MCR · 2026Article
- HSD3B1 links ileal steroid metabolism to bile acid regulation in patients with prostate cancer.The Journal of clinical investigation · 2026Article
- Serendipity, steroids and science.The Journal of steroid biochemistry and molecular biology · 2026Review
- Prostate cancer germline variants with therapeutic implications.Trends in molecular medicine · 2026Review
- Androgen metabolism in prostate cancer: recent advances.Endocrinology · 2026Review
- Emerging therapies to overcome antiandrogen resistance and beyond in lethal prostate cancer.Journal of the National Cancer Center · 2026Review
- SENP5 acts as a downstream target of androgen receptor and contributes to prostate cancer growth.Oncology letters · 2026Article
- A bypass gateway from cholesterol to sex steroid biosynthesis circumnavigates CYP17A1.Nature communications · 2025Article
- Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer.Nature genetics · 2025Article
- Utilizing a novel mitochondrial-related gene signature for predicting the prognosis and immunological impact in bladder cancer.Discover oncology · 2025Article
- Germline-Somatic Liaison Dictates Cancer Subtypes via de novo Steroid Biosynthesis.Cancer discovery · 2025Article
- New frontiers in prostate cancer treatment from systemic therapy to targeted therapy.EMBO molecular medicine · 2025Review
145 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
Growth of prostate cancer cells is dependent upon androgen stimulation of the androgen receptor (AR). Dihydrotestosterone (DHT), the most potent androgen, is usually synthesized in the prostate from testosterone secreted by the testis. Following chemical or surgical castration, prostate cancers usually shrink owing to testosterone deprivation. However, tumors often recur, forming castration-resistant prostate cancer (CRPC). Here, we show that CRPC sometimes expresses a gain-of-stability mutation that leads to a gain-of-function in 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1), which catalyzes the initial rate-limiting step in conversion of the adrenal-derived steroid dehydroepiandrosterone to DHT. The mutation (N367T) does not affect catalytic function, but it renders the enzyme resistant to ubiquitination and degradation, leading to profound accumulation. Whereas dehydroepiandrosterone conversion to DHT is usually very limited, expression of 367T accelerates this conversion and provides the DHT necessary to activate the AR. We suggest that 3βHSD1 is a valid target for the treatment of CRPC.
Indexed as
Identifiers
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.