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Effect of Omomyc treatment on human TNBC MDAMB231 cell line

ABSTRACT: Effect of Omomyc treatment on human TNBC MDAMB231 cell line

PROVIDER: PRJNA729983 | ENA |

REPOSITORIES: ENA

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Effect of Omomyc treatment on human TNBC MDAMB231 cell line

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Effect of Omomyc in vivo treatment on lung adenocarcinoma of KRasLSL-G12D/+ transgenic mouse

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MYC inhibition by Omomyc causes DNA damage and overcomes PARPi resistance in breast cancer.

Project description:MYC is dysregulated in most human cancers and is a DNA damage response (DDR) modulator capable of both promoting genomic instability and enhancing DNA repair. Here, we show that Omomyc, the first direct MYC inhibitor to pass a Phase 1 trial, shuts down DDR genes in triple-negative breast cancer (TNBC), causing DDR defects and inducing DNA damage. Since DDR-deficient tumours are currently targeted by PARP inhibitors (PARPi), we tested combinations with Omomyc. We show that Omomyc-induced DNA damage is enhanced by PARPi and that the inhibitors cooperate even in models with intrinsic or acquired PARPi resistance, both in vitro and in vivo. Moreover, using patient-derived models and clinical samples, we reveal a role for MYC as a predictor of PARPi resistance. Overall, our research highlights the opportunity of combining MYC inhibition by Omomyc with PARPi in PARPi-resistant TNBC, where MYC transcriptional activity represents a predictive biomarker of resistance to therapy.

2025-09-26 | GSE309250 | GEO

Effect of Omomyc on lymph node metastases from melanomas [SkMel147]

Project description:Skin melanomas are highly aggressive and metastatic. Omomyc is the best MYC inhibitor currently available. We analysed the effect of Omomyc expression in a transgenic and inducible (upon Doxycycline addition) manner in spontaneous lymph node metastases from SkMel147 (mutated in NRAS) melanoma cells in vivo. We used microarrays to detail the change in the gene expression programs induced by Omomyc on day 2.

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