ArticleEuropean urology2020
Durable Response of Enzalutamide-resistant Prostate Cancer to Supraphysiological Testosterone Is Associated with a Multifaceted Growth Suppression and Impaired DNA Damage Response Transcriptomic Program in Patient-derived Xenografts.
Article in European urology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Advances in sequencing and omics studies in prostate cancer: unveiling molecular pathogenesis and clinical applications.Frontiers in oncology · 2024Pooled it
- Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review.Frontiers in endocrinology · 2022Pooled it
- Bipolar androgen therapy plus nivolumab for patients with metastatic castration-resistant prostate cancer: the COMBAT phase II trial.Nature communications · 2024Trial
- ANXA2-mediated Phagocytosis Generates ARAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reprogramming of Androgen Receptor Activity in Castration-resistant Prostate Cancer is Shaped by Truncated Variants.European urology focus · 2025Article
- Two Decades of Disease Evolution and Biomarker-Guided Clinical Decision Making in Metastatic Prostate Cancer.International journal of molecular 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
- Effective therapeutic targeting of tumor lineage plasticity in neuroendocrine prostate cancer by BRD4 inhibitors.Acta pharmaceutica Sinica. B · 2025Article
- Functional inversion of circadian regulator REV-ERBα leads to tumorigenic gene reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Acetylated KHSRP impairs DNA-damage-response-related mRNA decay and facilitates prostate cancer tumorigenesis.Molecular oncology · 2024Article
- Genomic and transcriptomic features of androgen receptor signaling inhibitor resistance in metastatic castration-resistant prostate cancer.The Journal of clinical investigation · 2024Article
- Metastatic Bladder Cancer Expression and Subcellular Localization of Nectin-4 and Trop-2 in Variant Histology: A Rapid Autopsy Study.Clinical genitourinary cancer · 2023Article
- Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor through cMYC Repression and Recruitment of the DREAM Complex.Cancer research · 2023Article
- The future of patient-derived xenografts in prostate cancer research.Nature reviews. Urology · 2023Review
- The testosterone paradox of advanced prostate cancer: mechanistic insights and clinical implications.Nature reviews. Urology · 2023Review
- A kinome-wide CRISPR screen identifies CK1α as a target to overcome enzalutamide resistance of prostate cancer.Cell reports. Medicine · 2023Article
- A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance.Science advances · 2023Article
- Bipolar androgen therapy plus olaparib in men with metastatic castration-resistant prostate cancer.Prostate cancer and prostatic diseases · 2023Article
- Androgen receptor activity in prostate cancer dictates efficacy of bipolar androgen therapy through MYC.The Journal of clinical investigation · 2022Article
- Therapeutic Implications for Intrinsic Phenotype Classification of Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundAndrogen deprivation therapy improves the survival of castration-resistant prostate cancer (CRPC) patients, yet ultimately fails with debilitating side effects. Supraphysiological testosterone (SPT)-based therapy produces clinical responses with improved quality of life in a subset of patients. Currently, no information defines a durable response to SPT.
objectiveTo identify key molecular phenotypes underlying SPT response to improve patient selection and guide combination treatment to achieve a durable response. DESIGN, SETTING, AND
participantsA patient-derived xenograft (PDX) preclinical trial was performed with 13 CRPC PDXs to identify molecular features associated with SPT response. Comprehensive intratumoral androgen, tumor growth, and integrated transcriptomic and protein analyses were performed in three PDXs resistant to the newer androgen receptor (AR) pathway inhibitor enzalutamide (ENZ) to define SPT response and resistance.
interventionTestosterone cypionate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: SPT efficacy was evaluated by PDX growth, prostate-specific antigen (PSA) change, and survival. Intratumoral androgens were analyzed using mass spectrometry. Global transcriptome analysis was performed using RNA sequencing, and confirmed by quantitative real-time polymerase chain reaction and immunohistochemistry. Log-rank and Mann-Whitney tests were used for survival and molecular analyses, respectively. RESULTS AND LIMITATIONS: A durable SPT responder was identified, presenting robust repressions of ARv7 and E2F transcriptional outputs, and a DNA damage response (DDR) transcriptomic program that were altogether restored upon SPT resistance in the transient responder. ENZ rechallenge of SPT-relapsed PDXs resulted in PSA decreases but tumor progression.
conclusionsSPT produces a durable response in AR-pathway inhibitor ENZ CRPC that is associated with sustained suppression of ARv7 and E2F transcriptional outputs, and the DDR transcriptome, highlighting the potential of combination treatments that maintain suppression of these programs to drive a durable response to SPT. PATIENT SUMMARY: Patients with ENZ-resistant prostate cancer have very limited treatment options. Supraphysiological testosterone presents a prominent option for improved quality of life and a potential durable response in patients with sustained suppression on ARv7/E2F transcriptional outputs and DNA repair program.
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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.