2018
Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS
Kitajima S, Asahina H, Chen T, Guo S, Quiceno L, Cavanaugh J, Merlino A, Tange S, Terai H, Kim J, Wang X, Zhou S, Xu M, Wang S, Zhu Z, Thai T, Takahashi C, Wang Y, Neve R, Stinson S, Tamayo P, Watanabe H, Kirschmeier P, Wong K, Barbie D. Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS. Cancer Cell 2018, 34: 439-452.e6. PMID: 30205046, PMCID: PMC6422029, DOI: 10.1016/j.ccell.2018.08.009.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsAntineoplastic Agents, ImmunologicalCarcinoma, Non-Small-Cell LungCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmHEK293 CellsHumansImmunity, InnateInsulin-Like Growth Factor ILung NeoplasmsMiceMice, TransgenicMitogen-Activated Protein Kinase KinasesPhosphoproteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)Transcription FactorsYAP-Signaling ProteinsConceptsGenetically engineered mouse modelsMediators of acquired resistanceDownstream of KRASBET inhibitor JQ1Effective therapeutic strategyTumor shrinkageTargeted therapyIntermittent treatmentYAP1 signalingMouse modelPathway inhibitionBET inhibitionTherapeutic strategiesInhibitor JQ1YAP1 upregulationOncogenic KRASBET inhibitorsOvercome resistancePromoter acetylationIntrinsic resistancePotential translationKRASMEKInnateInhibition
2017
KEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer
Krall E, Wang B, Munoz D, Ilic N, Raghavan S, Niederst M, Yu K, Ruddy D, Aguirre A, Kim J, Redig A, Gainor J, Williams J, Asara J, Doench J, Janne P, Shaw A, McDonald R, Engelman J, Stegmeier F, Schlabach M, Hahn W. KEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer. ELife 2017, 6: e18970. PMID: 28145866, PMCID: PMC5305212, DOI: 10.7554/elife.18970.Peer-Reviewed Original ResearchConceptsALK inhibitionMAPK signalingResponse to BRAFLoss of Keap1Presence of multiple inhibitorsAltering cell metabolismLung cancer cellsResistant to inhibitionClinical responseDeletion screeningTargeted therapyRTK/Ras/MAPK pathwayNegative regulatorReactive oxygen speciesCell metabolismCancer cellsBRAFCancerous inhibitorMultiple inhibitorsEGFRKEAP1 lossPromote survivalKeap1/Nrf2 pathwayOxygen speciesALK