ArticleThe Prostate2019
Effective targeting of RNA polymerase I in treatment-resistant prostate cancer.
Article in The Prostate, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- In vivo CRISPR knockout screen identifies Polr1a as a key driver and a potential therapeutic target for melanoma metastasis.Oncogene · 2026Article
- Ubiquitination of Oncogenic Mutant p53 via Attenuation of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth.Molecular cancer therapeutics · 2026Article
- Combined MYC Activation and PTEN Loss Drives Molecular Features of Aggressive Preinvasive Lesions in Mouse Prostate.Molecular cancer research : MCR · 2026Article
- Ribosomal RNA transcription regulates splicing through ribosomal protein RPL22.Cell chemical biology · 2025Article
- Ribosomal RNA Biosynthesis Functionally Programs Tumor-Associated Macrophages to Support Breast Cancer Progression.Cancer research · 2025Article
- Article
- CACYBP knockdown inhibits progression of prostate cancer via p53.Journal of cancer research and clinical oncology · 2023Article
- Small molecule-mediated disruption of ribosome biogenesis synergizes with FGFR inhibitors to suppress glioma cell growth.Neuro-oncology · 2023Article
- Regulation of RNA Polymerase I Stability and Function.Cancers · 2022Review
- Ribosome-Directed Therapies in Cancer.Biomedicines · 2022Review
- Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance.Cancer research · 2022Review
- Review
- A high-throughput assay for directly monitoring nucleolar rRNA biogenesis.Open biology · 2022Article
- Zinc finger C3H1 domain-containing protein (ZFC3H1) evaluates the prognosis and treatment of prostate adenocarcinoma (PRAD): A study based on TCGA data.Bioengineered · 2021Article
- The role of OncoSnoRNAs and Ribosomal RNA 2'-O-methylation in Cancer.RNA biology · 2021Review
- Antagonising Chromatin Remodelling Activities in the Regulation of Mammalian Ribosomal Transcription.Genes · 2021Review
- Stromal CAVIN1 Controls Prostate Cancer Microenvironment and Metastasis by Modulating Lipid Distribution and Inflammatory Signaling.Molecular cancer research : MCR · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAdvanced prostate cancers depend on protein synthesis for continued survival and accelerated rates of metabolism for growth. RNA polymerase I (Pol I) is the enzyme responsible for ribosomal RNA (rRNA) transcription and a rate-limiting step for ribosome biogenesis. We have shown using a specific and sensitive RNA probe for the 45S rRNA precursor that rRNA synthesis is increased in prostate adenocarcinoma compared to nonmalignant epithelium. We have introduced a first-in-class Pol I inhibitor, BMH-21, that targets cancer cells of multiple origins, and holds potential for clinical translation.
methodsThe effect of BMH-21 was tested in prostate cancer cell lines and in prostate cancer xenograft and mouse genetic models.
resultsWe show that BMH-21 inhibits Pol I transcription in metastatic, castration-resistant, and enzalutamide treatment-resistant prostate cancer cell lines. The genetic abrogation of Pol I effectively blocks the growth of prostate cancer cells. Silencing of p53, a pathway activated downstream of Pol I, does not diminish this effect. We find that BMH-21 significantly inhibited tumor growth and reduced the Ki67 proliferation index in an enzalutamide-resistant xenograft tumor model. A decrease in 45S rRNA synthesis demonstrated on-target activity. Furthermore, the Pol I inhibitor significantly inhibited tumor growth and pathology in an aggressive genetically modified Hoxb13-MYC|Hoxb13-Cre|Pten
conclusionTaken together, BMH-21 is a novel promising molecule for the treatment of castration-resistant prostate cancer.
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