ArticleThe Journal of clinical investigation2019
Supraphysiological androgens suppress prostate cancer growth through androgen receptor-mediated DNA damage.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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
73 citing papers in PubMed, 106 citations in OpenAlex.
- Bipolar androgen therapy plus nivolumab for patients with metastatic castration-resistant prostate cancer: the COMBAT phase II trial.Nature communications · 2024Trial
- Bipolar androgen therapy sensitizes castration-resistant prostate cancer to subsequent androgen receptor ablative therapy.European journal of cancer (Oxford, England : 1990) · 2021Trial
- DNA-PKcs and PARP1 at the interface between DNA damage responses and cGAS-STING signaling: context-dependent roles and therapeutic implications.Cancer biology & therapy · 2026Review
- Beyond androgen deprivation therapy: Next-generation hormonal therapies and emerging combination approaches in advanced prostate cancer.Urologic oncology · 2026Review
- Intratumoral androstene-3,17-dione defines breast cancer subtype and prognosis.EMBO molecular medicine · 2026Article
- Bipolar Androgen Therapy as a Potential Mechanistic Bridge to Enhance PARP Inhibitor Efficacy in Prostate Cancer.The Kaohsiung journal of medical sciences · 2026Article
- A Spatiotemporal Atlas of the Androgen Receptor Proximal Interactome.bioRxiv : the preprint server for biology · 2026Article
- Lack of synergy between AR-targeted therapies and PARP inhibitors in homologous recombination-proficient prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance.Journal of the National Cancer Center · 2026Review
- Emerging therapies to overcome antiandrogen resistance and beyond in lethal prostate cancer.Journal of the National Cancer Center · 2026Review
- Mechanisms and progress of LncRNAs in prostate cancer development and diagnostic therapy.International urology and nephrology · 2025Review
- Review
- Evolving roles for the androgen receptor and its protein interactome in castration-resistant prostate cancer.Oncogene · 2025Review
- New frontiers in prostate cancer treatment from systemic therapy to targeted therapy.EMBO molecular medicine · 2025Review
- Article
- PSA/testosterone ratio as a potential biomarker to identify early progressors of adaptive therapy in metastatic castration sensitive prostate cancer.medRxiv : the preprint server for health sciences · 2025Article
- Heterogeneous Responses to High-Dose Testosterone in Castration-Resistant Prostate Cancer Tumors with Mixed Rb-Proficient and Rb-Deficient Cells.Molecular cancer therapeutics · 2025Article
- Multi-omics analysis constructs a novel neuroendocrine prostate cancer classifier and classification system.Scientific reports · 2025Article
- Article
- Evaluation of Adrenal Metastases in Prostate Cancer Patients with [68GA]GA-PSMA PET/CT Imaging.Current oncology (Toronto, Ont.) · 2025Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Prostate cancer (PC) is initially dependent on androgen receptor (AR) signaling for survival and growth. Therapeutics designed to suppress AR activity serve as the primary intervention for advanced disease. However, supraphysiological androgen (SPA) concentrations can produce paradoxical responses leading to PC growth inhibition. We sought to discern the mechanisms by which SPA inhibits PC and to determine if molecular context associates with anti-tumor activity. SPA produced an AR-mediated, dose-dependent induction of DNA double-strand breaks (DSBs), G0/G1 cell cycle arrest and cellular senescence. SPA repressed genes involved in DNA repair and delayed the restoration of damaged DNA which was augmented by PARP1 inhibition. SPA-induced DSBs were accentuated in BRCA2-deficient PCs, and combining SPA with PARP or DNA-PKcs inhibition further repressed growth. Next-generation sequencing was performed on biospecimens from PC patients receiving SPA as part of ongoing Phase II clinical trials. Patients with mutations in genes mediating homology-directed DNA repair were more likely to exhibit clinical responses to SPA. These results provide a mechanistic rationale for directing SPA therapy to PCs with AR amplification or DNA repair deficiency, and for combining SPA therapy with PARP inhibition.
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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.