Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers. Academic Article uri icon

Overview

abstract

  • The majority of human breast cancer is estrogen receptor alpha (ER) positive. While anti-estrogens/aromatase inhibitors are initially effective, resistance to these drugs commonly develops. Therapy-resistant tumors often retain ER signaling, via interaction with critical oncogenic coregulator proteins. To address these mechanisms of resistance, we have developed a novel ER coregulator binding modulator, ERX-11. ERX-11 interacts directly with ER and blocks the interaction between a subset of coregulators with both native and mutant forms of ER. ERX-11 effectively blocks ER-mediated oncogenic signaling and has potent anti-proliferative activity against therapy-sensitive and therapy-resistant human breast cancer cells. ERX-11 is orally bioavailable, with no overt signs of toxicity and potent activity in both murine xenograft and patient-derived breast tumor explant models. This first-in-class agent, with its novel mechanism of action of disrupting critical protein-protein interactions, overcomes the limitations of current therapies and may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers.

publication date

  • August 8, 2017

Research

keywords

  • Breast Neoplasms
  • Estrogen Receptor Antagonists
  • Receptors, Estrogen

Identity

PubMed Central ID

  • PMC5548489

Scopus Document Identifier

  • 85029221167

Digital Object Identifier (DOI)

  • 10.1126/science.279.5358.1922

PubMed ID

  • 28786813

Additional Document Info

volume

  • 6