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Transcriptional profiling of EZM8266 treatment in a syngeneic model of PARPi-resistant ovarian cancer.

GSE268078 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2024/12/18 Platform GPL34328
Summary
Euchromatin methyltransferase1/2 (EHMT1/2) have been correlated with tumorigenesis and therapy resistance through unknown mechanisms of action. Using a combination of experimental and bioinformatic analyses in several PARP inhibitor resistant ovarian cancer models, we demonstrate that combinatory EHMT and PARP inhibition is effective in treating PARP inhibitor resistant ovarian cancers. Our in vitro studies show that combinatory therapy reactivates transposable elements and increased immunostimulatory dsRNA formation and several immune signaling pathways. Our in vivo studies show that single EHMT and combinatory EHMT and PARP inhibition reduces tumor burden and that this reduction is dependent on CD8 T cells. Together, our results show a direct mechanism by which transposable elements are regulated and how an epigenetic therapy can be used as a fine tune agent to treat cancers with specific genetics.
Published in
EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell-Dependent Manner
Nguyen LL, Watson ZL, Ortega R et al. · Molecular cancer research : MCR 2024 · PMID 39136655 · doi:10.1158/1541-7786.MCR-24-0067
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Also filed as BioProject PRJNA1114461 and SRA study SRP509144. Searching any of these in the dataset finder brings you back here.

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