ArticleClinical cancer research : an official journal of the American Association for Cancer Research2018
Strategy for Tumor-Selective Disruption of Androgen Receptor Function in the Spectrum of Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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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
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Androgen receptor variant-driven prostate cancer II: advances in clinical investigation.Prostate cancer and prostatic diseases · 2020Pooled it
- Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations.Prostate cancer and prostatic diseases · 2020Pooled it
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- Poly(ADP-ribose) Polyremase-1 (PARP-1) Inhibition: A Promising Therapeutic Strategy for ETS-Expressing Tumours.International journal of molecular sciences · 2023Review
- The Small Molecule Antagonist KCI807 Disrupts Association of the Amino-Terminal Domain of the Androgen Receptor with ELK1 by Modulating the Adjacent DNA Binding Domain.Molecular pharmacology · 2023Article
- Role of ELK1 in regulating colorectal cancer progression: miR-31-5p/CDIP1 axis in CRC pathogenesis.PeerJ · 2023Article
- Identification of ELK1 interacting peptide segments in the androgen receptor.The Biochemical journal · 2022Article
- Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development.International journal of molecular sciences · 2021Review
- ELK1 Promotes Epithelial-Mesenchymal Transition and the Progression of Lung Adenocarcinoma by Upregulating B7-H3.Oxidative medicine and cellular longevity · 2021Article
- The ternary complex factor protein ELK1 is an independent prognosticator of disease recurrence in prostate cancer.The Prostate · 2020Article
- De-ubiquitination of ELK-1 by USP17 potentiates mitogenic gene expression and cell proliferation.Nucleic acids research · 2019Article
- Targeting ELK1: a wELKome addition to the prostate cancer armamentarium.AME medical journal · 2018Article
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Authors and funding
17 authors at 4 institutions in 4 countries.
Funding
Abstract
purposeTestosterone suppression in prostate cancer is limited by serious side effects and resistance via restoration of androgen receptor (AR) functionality. ELK1 is required for AR-dependent growth in various hormone-dependent and castration-resistant prostate cancer models. The amino-terminal domain of AR docks at two sites on ELK1 to coactivate essential growth genes. This study explores the ability of small molecules to disrupt the ELK1-AR interaction in the spectrum of prostate cancer, inhibiting AR activity in a manner that would predict functional tumor selectivity. EXPERIMENTAL
designSmall-molecule drug discovery and extensive biological characterization of a lead compound.
resultsWe have discovered a lead molecule (KCI807) that selectively disrupts ELK1-dependent promoter activation by wild-type and variant ARs without interfering with ELK1 activation by ERK. KCI807 has an obligatory flavone scaffold and functional hydroxyl groups on C5 and C3'. KCI807 binds to AR, blocking ELK1 binding, and selectively blocks recruitment of AR to chromatin by ELK1. KCI807 primarily affects a subset of AR target growth genes selectively suppressing AR-dependent growth of prostate cancer cell lines with a better inhibitory profile than enzalutamide. KCI807 also inhibits
conclusionsThe results offer a mechanism-based therapeutic paradigm for disrupting the AR growth-promoting axis in the spectrum of prostate tumors while reducing global suppression of testosterone actions. KCI807 offers a good lead molecule for drug development.
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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.