ArticleScientific reports2016
Targeting of CYP17A1 Lyase by VT-464 Inhibits Adrenal and Intratumoral Androgen Biosynthesis and Tumor Growth of Castration Resistant Prostate Cancer.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 40 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
- Exploring the Potential of Sulfur Moieties in Compounds Inhibiting Steroidogenesis.Biomolecules · 2023Article
- Acetyl-CoA Counteracts the Inhibitory Effect of Antiandrogens on Androgen Receptor Signaling in Prostate Cancer Cells.Cancers · 2022Article
- Advances in the Current Understanding of the Mechanisms Governing the Acquisition of Castration-Resistant Prostate Cancer.Cancers · 2022Review
- The androgen receptor is a therapeutic target in desmoplastic small round cell sarcoma.Nature communications · 2022Article
- A synthesis of a rationally designed inhibitor of cytochrome P450 8B1, a therapeutic target to treat obesity.Steroids · 2022Article
- Activity of Combined Androgen Receptor Antagonism and Cell Cycle Inhibition in Androgen Receptor Positive Triple Negative Breast Cancer.Molecular cancer therapeutics · 2021Article
- Review
- The role of adrenal derived androgens in castration resistant prostate cancer.The Journal of steroid biochemistry and molecular biology · 2020Review
- Recent Discoveries in the Androgen Receptor Pathway in Castration-Resistant Prostate Cancer.Frontiers in oncology · 2020Review
- High throughput metabolomics-proteomics investigation on metabolic phenotype changes in rats caused byRSC advances · 2019Article
- Assessing Therapeutic Efficacy in Real-time by Hyperpolarized Magnetic Resonance Metabolic Imaging.Cells · 2019Review
- Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Alters Hyperpolarized Pyruvate to Lactate Conversion and Lactate Levels In Vivo.Molecular imaging and biology · 2019Article
- Metastatic prostate cancer remains incurable, why?Asian journal of urology · 2019Review
- Functional characterization of the G162R and D216H genetic variants of human CYP17A1.The Journal of steroid biochemistry and molecular biology · 2018Article
- Inhibition ofJournal of Cancer · 2018Article
- Precision medicine applications in prostate cancer.Therapeutic advances in medical oncology · 2018Review
- Androgen receptor antagonism and impact on inhibitors of androgen synthesis in prostate cancer therapy.Translational cancer research · 2017Article
- Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer.The Journal of clinical investigation · 2017Article
- Lineage plasticity-mediated therapy resistance in prostate cancer.Asian journal of andrologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a validated treatment target for the treatment of metastatic castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) inhibits both 17α-hydroxylase (hydroxylase) and 17,20-lyase (lyase) reactions catalyzed by CYP17A1 and thus depletes androgen biosynthesis. However, coadministration of prednisone is required to suppress the mineralocorticoid excess and cortisol depletion that result from hydroxylase inhibition. VT-464, a nonsteroidal small molecule, selectively inhibits CYP17A1 lyase and therefore does not require prednisone supplementation. Administration of VT-464 in a metastatic CRPC patient presenting with high tumoral expression of both androgen receptor (AR) and CYP17A1, showed significant reduction in the level of both dehydroepiandrosterone (DHEA) and serum PSA. Treatment of a CRPC patient-derived xenograft, MDA-PCa-133 expressing H874Y AR mutant with VT-464, reduced the increase in tumor volume in castrate male mice more than twice as much as the vehicle (P < 0.05). Mass spectrometry analysis of post-treatment xenograft tumor tissues showed that VT-464 significantly decreased intratumoral androgens but not cortisol. VT-464 also reduced AR signaling more effectively than abiraterone in cultured PCa cells expressing T877A AR mutant. Collectively, this study suggests that VT-464 therapy can effectively treat CRPC and be used in precision medicine based on androgen receptor mutation status.
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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.