title: Molecular pathways: targeting ETS gene fusions in cancer.
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.
authors: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan. Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan. Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Felix Y
authors: FY
authors: Feng
authors: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan. Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan. Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan.
authors: J Chad
authors: JC
authors: Brenner
authors: Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan. Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, Michigan. Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Maha
authors: M
authors: Hussain
authors: arul@umich.edu.
authors: Arul M
authors: AM
authors: Chinnaiyan
mesh_terms: D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D051747:DNA-Activated Protein Kinase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D050939:Gene Fusion / Q000235:genetics*; D056284:Histone Deacetylase 1 / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C556015:PARPBP protein, human; D050783:Proto-Oncogene Proteins c-ets; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1