Activation of endogenous retroviruses and induction of viral mimicry by MEK1/2 inhibition in pancreatic cancer

While pancreatic ductal adenocarcinomas (PDAC) are addicted to KRAS-activating mutations, inhibitors of downstream effectors in the KRAS pathway, such as the clinically approved MEK1/2 kinases inhibitor Trametinib, are devoid of significant therapeutic effects. Nevertheless, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway can induce novel functional states and vulnerabilities of potential therapeutic relevance. Here, we performed a quantitative histone post-translatinal modification analysis of PDAC cells in the initial hours after MEK1/2 inhibition by Trametinib.