ArticleThe Journal of clinical investigation2023
BMX controls 3βHSD1 and sex steroid biosynthesis in cancer.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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
21 citing papers in PubMed, 25 citations in OpenAlex.
- HSD3B1 genotype and outcomes in metastatic hormone-sensitive prostate cancer with androgen deprivation therapy and enzalutamide: ARCHES.Cell reports. Medicine · 2024Trial
- Targeting the BMX in cancer: molecular mechanisms and emerging therapeutic strategies.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- 3beta-HSD1-mediated steroid back-conversion maintains androgen signaling in prostate cancer.Molecular cancer research : MCR · 2026Article
- Riding toward Selectivity: Optimization of Covalent 7-Azaindole-Based BMX Kinase Inhibitors.Journal of medicinal chemistry · 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
- HSD3B1, prostate cancer mortality and modifiable outcomes.Nature reviews. Urology · 2025Review
- Machine learning-based transcriptmics analysis revealsFrontiers in pharmacology · 2025Article
- Elevated periprostatic androgens, sneaky testosterone and its implications.Nature reviews. Urology · 2024Review
- Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment.Expert review of anticancer therapy · 2024Review
- Androgen production, uptake, and conversion (APUC) genes define prostate cancer patients with distinct clinical outcomes.JCI insight · 2024Article
- Survival of men with metastatic hormone-sensitive prostate cancer and adrenal-permissive HSD3B1 inheritance.The Journal of clinical investigation · 2024Article
- Survival of men with metastatic hormone-sensitive prostate cancer and adrenal-permissive HSD3B1 inheritance.The Journal of clinical investigation · 2024Article
- TRIM26 inhibits clear cell renal cell carcinoma progression through destabilizing ETK and thus inactivation of AKT/mTOR signaling.Journal of translational medicine · 2024Article
- Adrenal-Permissive HSD3B1 Genotype-An Invisible Stimulator of Prostate Cancer Mortality.JAMA network open · 2024Article
- Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression.Cell reports · 2024Article
- Active DHEA uptake in the prostate gland correlates with aggressive prostate cancer.The Journal of clinical investigation · 2023Article
- Targeting the Androgen Signaling Axis in Prostate Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Review
- A phosphorylation switch controls androgen biosynthesis in prostate cancer.The Journal of clinical investigation · 2023Article
Corrections and comments
- Commented on byUro-Science.2023
Authors and funding
13 authors at 2 institutions in 4 countries.
Funding
Abstract
Prostate cancer is highly dependent on androgens and the androgen receptor (AR). Hormonal therapies inhibit gonadal testosterone production, block extragonadal androgen biosynthesis, or directly antagonize AR. Resistance to medical castration occurs as castration-resistant prostate cancer (CRPC) and is driven by reactivation of the androgen-AR axis. 3β-hydroxysteroid dehydrogenase-1 (3βHSD1) serves as the rate-limiting step for potent androgen synthesis from extragonadal precursors, thereby stimulating CRPC. Genetic evidence in men demonstrates the role of 3βHSD1 in driving CRPC. In postmenopausal women, 3βHSD1 is required for synthesis of aromatase substrates and plays an essential role in breast cancer. Therefore, 3βHSD1 lies at a critical junction for the synthesis of androgens and estrogens, and this metabolic flux is regulated through germline-inherited mechanisms. We show that phosphorylation of tyrosine 344 (Y344) occurs and is required for 3βHSD1 cellular activity and generation of Δ4, 3-keto-substrates of 5α-reductase and aromatase, including in patient tissues. BMX directly interacts with 3βHSD1 and is necessary for enzyme phosphorylation and androgen biosynthesis. In vivo blockade of 3βHSD1 Y344 phosphorylation inhibits CRPC. These findings identify what we believe to be new hormonal therapy pharmacologic vulnerabilities for sex-steroid dependent cancers.
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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.