ArticleScientific reports2019
Drivers of AR indifferent anti-androgen resistance in prostate cancer cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The trial behind it
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Who cites it
49 citing papers in PubMed, 73 citations in OpenAlex.
- Epigenetic profiling identifies markers of endocrine resistance and therapeutic options for metastatic castration-resistant prostate cancer.Cell reports. Medicine · 2025Trial
- Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance.Proceedings of the National Academy of Sciences of the United States of America · 2020Trial
- Development and Characterization of the PSMA-Expressing CT26-PSMA Cell Line as a Rapid Preclinical Platform forInternational journal of molecular sciences · 2026Article
- Integrative transcriptomic profiling reveals subtype-specific therapeutic vulnerabilities and resistance mechanisms in prostate cancer.BMC cancer · 2026Article
- Developing therapeutic strategies to target MCL1 and BCLXL in lethal prostate cancer.iScience · 2025Article
- STARD4 suppresses tumorigenesis and attenuates enzalutamide resistance via lipid metabolic reprogramming and AR stabilization in prostate cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Simultaneous inhibition of TRIM24 and TRIM28 sensitises prostate cancer cells to antiandrogen therapy, decreasing VEGF signalling and angiogenesis.Molecular oncology · 2025Article
- Detection of Genome-Wide IGF-1R Recruitment to Enhancer and Promoter Regions of Chromatin in Clinical Prostate Cancers.Cancer medicine · 2025Article
- Transcriptional profiling clarifies a program of enzalutamide extreme non-response in lethal prostate cancer.NPJ precision oncology · 2025Article
- Chrysosplenetin B suppresses the growth of human prostate cancer cells by inducing G1 cell cycle arrest.BioImpacts : BI · 2025Article
- The impact of androgen-induced translation in modulating androgen receptor activity.Biology direct · 2024Article
- Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell Lines.Antioxidants (Basel, Switzerland) · 2024Article
- Computational drug discovery pipelines identify NAMPT as a therapeutic target in neuroendocrine prostate cancer.Clinical and translational science · 2024Article
- Neuroendocrine Prostate Cancer Drivers SOX2 and BRN2 Confer Differential Responses to Imipridones ONC201, ONC206, and ONC212 in Prostate Cancer Cell Lines.bioRxiv : the preprint server for biology · 2024Article
- Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients.Journal of experimental & clinical cancer research : CR · 2024Review
- Enzalutamide induces cytotoxicity in desmoplastic small round cell tumor independent of the androgen receptor.Communications biology · 2024Article
- Neuroendocrine prostate cancer drivers SOX2 and BRN2 confer differential responses to imipridones ONC201, ONC206, and ONC212 in prostate cancer cell lines.American journal of translational research · 2024Article
- Cardio-oncology in advanced prostate cancer.Frontiers in oncology · 2024Article
- Orexins and Prostate Cancer: State of the Art and Potential Experimental and Therapeutic Perspectives.Cancer genomics & proteomics · 2023Review
- Enzalutamide Induces Cytotoxicity in Desmoplastic Small Round Cell Tumor Independent of the Androgen Receptor.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of the androgen receptor (AR) by second-generation anti-androgens is a standard treatment for metastatic castration resistant prostate cancer (mCRPC), but it inevitably leads to the development of resistance. Since the introduction of highly efficient AR signalling inhibitors, approximately 20% of mCRPC patients develop disease with AR independent resistance mechanisms. In this study, we generated two anti-androgen and castration resistant prostate cancer cell models that do not rely on AR activity for growth despite robust AR expression (AR indifferent). They are thus resistant against all modern AR signalling inhibitors. Both cell lines display cross-resistance against the chemotherapeutic drug docetaxel due to MCL1 upregulation but remain sensitive to the PARP inhibitor olaparib and the pan-BCL inhibitor obatoclax. RNA-seq analysis of the anti-androgen resistant cell lines identified hyper-activation of the E2F cell-cycle master regulator as driver of AR indifferent growth, which was caused by deregulation of cyclin D/E, E2F1, RB1, and increased Myc activity. Importantly, mCRPC tissue samples with low AR activity displayed the same alterations and increased E2F activity. In conclusion, we describe two cellular models that faithfully mimic the acquisition of a treatment induced AR independent phenotype that is cross-resistant against chemotherapy and driven by E2F hyper-activation.
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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.