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Combination of MAPK pathway inhibitors dabrafenib/trametinib (MAPKi) with the HDAC3 inhibitor entinostat (HDACi) is highly efficacious against various sub-types of melanoma with BRAF, NRAS, PTEN and NF1 mutations expressing MGMT. Treatment of melanoma cells with the cocktail of MAPKi and HDACi suppresses expression of ELK transcription factors and impairs expression of genes involved in HR and NHEJ DSB repair pathways, potentiating DNA damage and cell death.
