2023
Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma
Chaudhary P, Xu X, Wang G, Hoj J, Rampersad R, Asselin-Labat M, Ting S, Kim W, Tamayo P, Pendergast A, Onaitis M. Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma. Cancer Research Communications 2023, 3: 2400-2411. PMID: 37882674, PMCID: PMC10668634, DOI: 10.1158/2767-9764.crc-22-0408.Peer-Reviewed Original ResearchConceptsType II cellsLung adenocarcinomaDual-positive cellsII cellsKRAS-mutant lung adenocarcinomaDevelopment of novel targeted therapeuticsTumor-initiating cellsNotch signalingAlveolar type II cellsNovel targeted therapeuticsCell of originThree-dimensional organoid culturesSOX2 upregulationKRAS activationAdenocarcinomaMouse modelTherapeutic strategiesProliferation of cellsGain-of-functionRNA sequencing analysisTransplantation studiesCellular plasticityOrganoid culturesSOX2 levelsNotch pathway
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