Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells
Sevrin T, Imoto H, Robertson S, Rauch N, Dyn'ko U, Koubova K, Wynne K, Kolch W, Rukhlenko O, Kholodenko B. Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells. Cell Reports 2024, 43: 114710. PMID: 39240715, PMCID: PMC11474227, DOI: 10.1016/j.celrep.2024.114710.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaResistance to RAFResistant PDAC cellsPancreatic cancer cellsPancreatic ductal adenocarcinoma cell linesProtein expression profilesTumor-specific variationsIsogenic pairsCell-specific modelsConformational specificityERK signalingInhibitor combinationsERK pathwayKRAS mutationsTargeted therapyExpression profilesMEK inhibitorsDuctal adenocarcinomaCancer cellsKRAS mutantPhospho-ERKCell linesPDAC cellsCell viabilityDifferential sensitivity