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
2015
Abstract PR04: A melanoma transcriptional state distinction influences sensitivity to MAPK pathway inhibitors
Johannessen C, Konieczkowski D, Abudayyeh O, Kim J, Cooper Z, Piris A, Frederick D, Barzily-Rokni M, Straussman R, Haq R, Fisher D, Mesirov J, Hahn W, Flaherty K, Wargo J, Tamayo P, Garraway L. Abstract PR04: A melanoma transcriptional state distinction influences sensitivity to MAPK pathway inhibitors. Clinical Cancer Research 2015, 21: pr04-pr04. DOI: 10.1158/1557-3265.pms14-pr04.Peer-Reviewed Original ResearchBRAFV600-mutant melanomaMAPK pathway inhibitorsPathway inhibitorCell linesMelanocyte lineage transcription factor MITFPanel of melanoma cell linesResistance to MAPK pathway inhibitorsMAPK pathway inhibitionReceptor tyrosine kinase AXLDrug-resistant cell linesImprove cancer therapyTyrosine kinase AXLMelanoma cell linesSensitive cell linesNF-kB activationNF-kB signalingRAF/MEK inhibitionMelanoma patientsClinical responseTranscription factor MITFMalignant melanomaDrug susceptibilityAcquired resistancePatient biopsiesMEK inhibitors