Targeting the ERG oncogene with splice-switching oligonucleotides as a novel therapeutic strategy in prostate cancer

@article{Li2020TargetingTE,
  title={Targeting the ERG oncogene with splice-switching oligonucleotides as a novel therapeutic strategy in prostate cancer},
  author={Ling Li and Lisa Hobson and Laura Perry and Bethany Clark and Susan Heavey and Aiman Haider and Ashwin Narasimha Sridhar and Greg Shaw and John Kelly and Alex Freeman and Ian D Wilson and Hayley C. Whitaker and Elmar Nurmemmedov and Sebastian Oltean and Sean R Porazinski and Michael Ladomery},
  journal={British Journal of Cancer},
  year={2020},
  volume={123},
  pages={1024 - 1032}
}
The ERG oncogene, a member of the ETS family of transcription factor encoding genes, is a genetic driver of prostate cancer. It is activated through a fusion with the androgen-responsive TMPRSS2 promoter in 50% of cases. There is therefore significant interest in developing novel therapeutic agents that target ERG. We have taken an antisense approach and designed morpholino-based oligonucleotides that target ERG by inducing skipping of its constitutive exon 4. We designed antisense morpholino… 
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TLDR
Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein).
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
Findings have identified critical molecular mechanisms involving ERK-mediated ERG activation that could be exploited for therapeutic intervention in ERG-positive prostate cancers.
The oncogene ERG: a key factor in prostate cancer
TLDR
ERG’s structure and function is reviewed, and its role in prostate cancer is discussed, and potential new therapies that are based on targeting ERG are discussed.
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