2024
Targeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer
Murayama T, Nakayama J, Jiang X, Miyata K, Morris A, Cai K, Prasad R, Ma X, Efimov A, Belani N, Gerstein E, Tan Y, Zhou Y, Kim W, Maruyama R, Campbell K, Chen L, Yang Y, Balachandran S, Canadas I. Targeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer. Cancer Discovery 2024, 14: 468-491. PMID: 38189443, PMCID: PMC10905673, DOI: 10.1158/2159-8290.cd-23-0486.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerDExD/H-box helicase 9Cell lung cancerCold tumorsLung cancerResponse to immune-checkpoint blockadeInnate immunityEnhance immunotherapy efficacyImmune-checkpoint blockadeImmunogenic tumor microenvironmentImmunologically cold tumorsNucleic acid-sensing pathwaysActivate innate immunityAntitumor immunityImmunotherapy efficacyReplication stressTumor microenvironmentTumor growthViral mimicryTumorImmune responseCancer cellsInterferon responseCytoplasmic dsRNACancer
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
KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine
Stewart M, Tamayo P, Wilson A, Wang S, Chang Y, Kim J, Khabele D, Shamji A, Schreiber S. KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine. Cancer Research 2015, 75: 2897-2906. PMID: 25968887, PMCID: PMC4506246, DOI: 10.1158/0008-5472.can-14-2860.Peer-Reviewed Original ResearchConceptsOvarian cancer cellsCancer cellsOvarian cancerHigh-grade serous ovarian cancer cellsGenomic statusBiomarkers of drug responseBcl-2 family inhibitorsAntitumor response rateSerous ovarian cancer cellsTreated with decitabineInhibit DNA methylationBreast cancer cellsDownregulation of DNMT1DNA methyltransferase inhibitionKRAS statusDNA methylationPredictive biomarkersSolid tumorsMEK inhibitorsMEK/ERK phosphorylationDecitabineBcl-2Drug responseXenograft modelLow-gradeA Functional Landscape of Resistance to ALK Inhibition in Lung Cancer
Wilson FH, Johannessen CM, Piccioni F, Tamayo P, Kim JW, Van Allen EM, Corsello SM, Capelletti M, Calles A, Butaney M, Sharifnia T, Gabriel SB, Mesirov JP, Hahn WC, Engelman JA, Meyerson M, Root DE, Jänne PA, Garraway LA. A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer. Cancer Cell 2015, 27: 397-408. PMID: 25759024, PMCID: PMC4398996, DOI: 10.1016/j.ccell.2015.02.005.Peer-Reviewed Original ResearchConceptsFunctional genetic studiesG protein-coupled receptorsResistance driversALK inhibitionFunctional landscapeGenetic studiesLung cancer cellsALK inhibitor resistanceResistance pathwaysMechanisms of resistanceReceptor familyPKC activationPurinergic receptor familyPKC inhibitionCrizotinib-resistant ALKCancer cellsInhibitor resistanceGene signatureDependent mechanismLung cancerLung tumorsALK inhibitorsInhibitionALKMechanism
2014
KRAS and YAP1 Converge to Regulate EMT and Tumor Survival
Shao D, Xue W, Krall E, Bhutkar A, Piccioni F, Wang X, Schinzel A, Sood S, Rosenbluh J, Kim J, Zwang Y, Roberts T, Root D, Jacks T, Hahn W. KRAS and YAP1 Converge to Regulate EMT and Tumor Survival. Cell 2014, 158: 171-184. PMID: 24954536, PMCID: PMC4110062, DOI: 10.1016/j.cell.2014.06.004.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCell Cycle ProteinsCell SurvivalColonic NeoplasmsDrug Delivery SystemsDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionHCT116 CellsHumansLung NeoplasmsMicePhosphoproteinsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsSignal TransductionTranscription FactorsTranscriptional ActivationYAP-Signaling ProteinsConceptsEpithelial-mesenchymal transitionTranscriptional regulator of epithelial-mesenchymal transitionOncogenic Ras signalingColon cancer cell linesTranscriptional coactivator YAP1KRAS-dependent cellsRegulator of epithelial-mesenchymal transitionMurine lung cancer modelTranscriptional regulationCancer cell linesMutant allelesRas signalingTranscription factor FosOncogenic RasTranscriptional programsLung cancer modelRegulating epithelial-mesenchymal transitionMolecular basisOncogenic alleleCell transformationYAP1YAP1 signalingPromote survivalCancer cellsOncogenic dependency