Signosis/EGFR (A767_dupASV) stably expressing BaF3 cells/EL010NP/1 Ea

Description:

Epidermalgrowthfactorreceptor(EGFR)isacell-surfacereceptorwithintrinsicintracellularprotein-tyrosinekinase(TK)activity.LigandbindinginducesEGFRdimerizationandphosphorylation,leadingtotheactivationofEGFRsignalingpathway.Inseveralmalignanciessuchasnon-smallcelllungcancer(NSCLC),EGFRsignalingisderegulatedduetomutationsinEGFR,whichresultsinuncontrolledproliferationandmigrationoftumorcells.EGFRmutationscanleadto“oncogene-addicted”cancers,wherethetumorcellsdependonthemutatedEGFRforcellsurvivalandmalignantphenotype. OneofthemostcommonEGFRmutationsfoundinhumanpatientsisL858Rsubstitutioninexon21,withintheactivationloopofEGFR.PatientswiththismutationaresensitivetoEGFRtyrosinekinaseinhibitors(TKIs)suchasgefitiniborerlotinib,whereaspatientswithwildtypeEGFRarenotsensitivetoTKI.AnotherclinicallyrelevantmutationassociatedwithacquiredgefitinibanderlotinibresistanceisT790M,foundinexon20.CellsexpressingEGFRwithbothL858RandT790Mmutationsareresistanttoinducedapoptosisinthepresenceofgefitiniborerlotinib. 

Data:

Dose-dependentgrowthinhibitionofBaF3cellsharboringEGFRexon20insertionD770-N771insSVDmutation(EL-008),controlBa/F3cellline(EL-001)andEGFRexon20,A767-dupASVmutation(EL-010).Thecellsweretreatedwiththeindicateddoseoferlotinibfor72hoursandcellviabilitywasmeasuredusingSignosisCVCreagent.