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Updated: Feb 5, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

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Strategy for Tumor-Selective Disruption of Androgen Receptor Function in the Spectrum of Prostate Cancer

Rayna Rosati1, Lisa Polin1, Charles Ducker2

  • 1Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 7, 2018
PubMed
Abstract

Insights

Researchers identified a new molecule, KCI807, that disrupts the interaction between androgen receptor (AR) and ELK1, inhibiting prostate cancer growth. This targeted approach offers a promising therapeutic strategy with fewer side effects than current treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Prostate cancer treatment faces challenges with side effects and resistance due to androgen receptor (AR) functionality.
  • ELK1 is crucial for AR-dependent growth in various prostate cancer models, including hormone-dependent and castration-resistant types.
  • The amino-terminal domain of AR interacts with ELK1 to coactivate essential growth genes.

Purpose of the Study:

  • To explore small molecules that disrupt the ELK1-AR interaction in prostate cancer.
  • To inhibit AR activity selectively, predicting functional tumor selectivity.
  • To develop a novel therapeutic strategy for prostate cancer treatment.

Main Methods:

  • Small-molecule drug discovery and lead compound characterization.
  • Biological assays to assess the disruption of ELK1-AR interaction.
  • In vitro and in vivo studies using prostate cancer cell lines and xenografts.

Main Results:

  • A lead molecule, KCI807, was discovered that selectively disrupts ELK1-dependent promoter activation by wild-type and variant ARs.
  • KCI807 binds to AR, blocks ELK1 binding, and inhibits AR recruitment to chromatin by ELK1.
  • KCI807 selectively suppresses AR-dependent growth of prostate cancer cells and inhibits tumor xenograft growth, outperforming enzalutamide in some aspects.

Conclusions:

  • KCI807 represents a promising lead molecule for drug development in prostate cancer.
  • The study offers a mechanism-based therapeutic paradigm for disrupting the AR growth-promoting axis.
  • This approach aims to reduce global suppression of testosterone actions while targeting prostate tumors effectively.

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