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
2021
An expanded universe of cancer targets
Hahn W, Bader J, Braun T, Califano A, Clemons P, Druker B, Ewald A, Fu H, Jagu S, Kemp C, Kim W, Kuo C, McManus M, B. Mills G, Mo X, Sahni N, Schreiber S, Talamas J, Tamayo P, Tyner J, Wagner B, Weiss W, Gerhard D, Dancik V, Gill S, Hua B, Sharifnia T, Viswanathan V, Zou Y, Dela Cruz F, Kung A, Stockwell B, Boehm J, Dempster J, Manguso R, Vazquez F, Cooper L, Du Y, Ivanov A, Lonial S, Moreno C, Niu Q, Owonikoko T, Ramalingam S, Reyna M, Zhou W, Grandori C, Shmulevich I, Swisher E, Cai J, Chan I, Dunworth M, Ge Y, Georgess D, Grasset E, Henriet E, Knútsdóttir H, Lerner M, Padmanaban V, Perrone M, Suhail Y, Tsehay Y, Warrier M, Morrow Q, Nechiporuk T, Long N, Saultz J, Kaempf A, Minnier J, Tognon C, Kurtz S, Agarwal A, Brown J, Watanabe-Smith K, Vu T, Jacob T, Yan Y, Robinson B, Lind E, Kosaka Y, Demir E, Estabrook J, Grzadkowski M, Nikolova O, Chen K, Deneen B, Liang H, Bassik M, Bhattacharya A, Brennan K, Curtis C, Gevaert O, Ji H, Karlsson K, Karagyozova K, Lo Y, Liu K, Nakano M, Sathe A, Smith A, Spees K, Wong W, Yuki K, Hangauer M, Kaufman D, Balmain A, Bollam S, Chen W, Fan Q, Kersten K, Krummel M, Li Y, Menard M, Nasholm N, Schmidt C, Serwas N, Yoda H, Ashworth A, Bandyopadhyay S, Bivona T, Eades G, Oberlin S, Tay N, Wang Y, Weissman J. An expanded universe of cancer targets. Cell 2021, 184: 1142-1155. PMID: 33667368, PMCID: PMC8066437, DOI: 10.1016/j.cell.2021.02.020.Peer-Reviewed Original ResearchConceptsNon-oncogene dependenciesDiversity of therapeutic targetsSomatically altered genesCancer targetCancer allelesInfluence therapyCancer genomesGenomic characterizationTherapeutic strategiesAltered genesCancer featuresCancer genesClinical translationCancerCancer biologyTherapeutic targetTumorGenomeGenes
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
Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States
Kim J, Abudayyeh O, Yeerna H, Yeang C, Stewart M, Jenkins R, Kitajima S, Konieczkowski D, Medetgul-Ernar K, Cavazos T, Mah C, Ting S, Van Allen E, Cohen O, Mcdermott J, Damato E, Aguirre A, Liang J, Liberzon A, Alexe G, Doench J, Ghandi M, Vazquez F, Weir B, Tsherniak A, Subramanian A, Meneses-Cime K, Park J, Clemons P, Garraway L, Thomas D, Boehm J, Barbie D, Hahn W, Mesirov J, Tamayo P. Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States. Cell Systems 2017, 5: 105-118.e9. PMID: 28837809, PMCID: PMC5639711, DOI: 10.1016/j.cels.2017.08.002.Peer-Reviewed Original ResearchConceptsCellular statesActivated downstream of RasDownstream of RasGenomic hallmarksIndividual tumor samplesCancer genomesRas pathwayPrecision medicine paradigmPharmacological perturbationsGenetic alterationsFunctional consequencesTranscriptional signatureSystematic sequenceReference mapEffective disease modelsOncogenic alterationsRasComplex landscapeTumor samplesDisease modelsTherapeutic strategiesMedicine paradigmGenomeAlterationsFunctional state