Molecular pathways: targeting ETS gene fusions in cancer

Felix Y. Feng, J. Chad Brenner, Maha Hussain, Arul M. Chinnaiyan

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations

Abstract

Rearrangements, or gene fusions, involving the ETS family of transcription factors are common driving events in both prostate cancer and Ewing sarcoma. These rearrangements result in pathogenic expression of the ETS genes and trigger activation of transcriptional programs enriched for invasion and other oncogenic features. Although ETS gene fusions represent intriguing therapeutic targets, transcription factors, such as those comprising the ETS family, have been notoriously difficult to target. Recently, preclinical studies have demonstrated an association between ETS gene fusions and components of the DNA damage response pathway, such as PARP1, the catalytic subunit of DNA protein kinase (DNAPK), and histone deactylase 1 (HDAC1), and have suggested that ETS fusions may confer sensitivity to inhibitors of these DNA repair proteins. In this review, we discuss the role of ETS fusions in cancer, the preclinical rationale for targeting ETS fusions with inhibitors of PARP1, DNAPK, and HDAC1, as well as ongoing clinical trials targeting ETS gene fusions.

Original languageEnglish (US)
Pages (from-to)4442-4448
Number of pages7
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Volume20
Issue number17
DOIs
StatePublished - Sep 1 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Molecular pathways: targeting ETS gene fusions in cancer'. Together they form a unique fingerprint.

Cite this