Development of Small Molecule Inhibitors of the ERG Transcription Factor in Prostate Cancer

About Development of Small Molecule Inhibitors of the ERG Transcription Factor in Prostate Cancer

What this means to patients: These promising inhibitors of an important prostate cancer driver protein, once considered undruggable, will provide a new therapeutic agent for Lupron-resistant prostate cancer, both in early and late disease progression.

Synopsis: The transcription factor ERG, a protein that binds DNA and initiates gene expression, is an oncogenic driver in both hormone-sensitive and treatment-resistant prostate cancer. ERG has so far been considered undruggable. Dr. Wang and colleagues have designed small, cell-penetrating synthetic peptide molecules that function as potent inhibitors of ERG both in vitro and in vivo. The peptides specifically disrupt ERG-DNA interaction, prevent DNA damage and cell invasion and suppress tumor growth and metastasis in animal models of prostate cancer. Researchers propose to generate three-dimensional crystal structures of ERG in complex with these peptides, which will allow optimization of the ERG inhibitors by improving the pharmacology of these drug candidates.

Shaomeng Wang, PhD

University of Michigan

Co-investigators:

Arul Chinnaiyan, MD, PhD; Jeanne Stuckey, PhD; George Wang, PhD; Chao-Yie Yang, PhD; Bushra Ateeq, PhD, University of Michigan