2022
MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer
Yoshida R, Saigi M, Tani T, Springer B, Shibata H, Kitajima S, Mahadevan N, Campisi M, Kim W, Kobayashi Y, Thai T, Haratani K, Yamamoto Y, Sundararaman S, Knelson E, Vajdi A, Canadas I, Uppaluri R, Paweletz C, Miret J, Lizotte P, Gokhale P, Jänne P, Barbie D. MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer. Cancer Research 2022, 82: 4079-4092. PMID: 36066413, PMCID: PMC9627131, DOI: 10.1158/0008-5472.can-22-0770.Peer-Reviewed Original ResearchConceptsEGFR-mutant lung cancerEGFR-TKI-resistant cellsThird-generation EGFR tyrosine kinase inhibitorMET-amplifiedT cell responsesPemetrexed treatmentLung cancerCD8+ T cell immunogenicityEGFR-TKI treatment failureEGFR tyrosine kinase inhibitorsInhibit T cell responsesUpregulation of CD73Humanized mouse modelTyrosine kinase inhibitorsT-cell immunogenicityCell line studiesMET amplificationEGFR-TKIsTKI resistanceTreatment failureCancer immunogenicityCD73 inhibitionT cellsPemetrexedEnhanced immunogenicity
2020
Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Stern J, Hibshman G, Hu K, Ferrara S, Costello J, Kim W, Tamayo P, Cech T, Huang F. Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers. Molecular Cancer Research 2020, 18: 1050-1062. PMID: 32276990, PMCID: PMC8020009, DOI: 10.1158/1541-7786.mcr-19-1244.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorChromatin ImmunoprecipitationEpithelial-Mesenchymal TransitionExtracellular Signal-Regulated MAP KinasesGene Expression ProfilingGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMutationNeoplasmsPromoter Regions, GeneticSequence Analysis, RNASmall Molecule LibrariesTelomeraseTumor MicroenvironmentConceptsCell linesAnalysis of cell linesAdherens junction protein E-cadherinKnock-down experimentsExpression signaturesRAS pathway inhibitorsInhibition of MEK1Promoter mutationsSensitivity to specific drugsCatalytic subunit of telomeraseJunction protein E-cadherinProtein E-cadherinSubunit of telomeraseInvestigational treatment approachesMesenchymal transcription factorsPan-cancer analysisCatalytic subunitEpithelial-to-mesenchymal transitionTranscription factorsCell line growthMutantsPathway effectorsTERT mRNA expressionMAPK signalingProliferative immortality
2019
Modelling bistable tumour population dynamics to design effective treatment strategies
Akhmetzhanov A, Kim J, Sullivan R, Beckman R, Tamayo P, Yeang C. Modelling bistable tumour population dynamics to design effective treatment strategies. Journal Of Theoretical Biology 2019, 474: 88-102. PMID: 31077681, PMCID: PMC9534689, DOI: 10.1016/j.jtbi.2019.05.005.Peer-Reviewed Original ResearchConceptsDrug resistanceHeterogeneous tumorsTumor cellsTreatment strategiesDevelopment of optimal therapeutic strategiesEffects of targeted drugsBRAF-mutant melanomaProcess of tumor growthOptimal therapeutic strategyDrug resistance characteristicsHeterogeneous tumor cellsReverse drug resistanceActivated alternative pathwayEmergence of resistanceCancer treatment modalityEffective treatment strategiesDesigning effective treatment strategiesDrug holidayBRAF inhibitorsPeriodate treatmentDrug regimensTreatment modalitiesGenetic alterationsTumor growthDrug sensitivity
2017
Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations
Huang F, Mosquera J, Garofalo A, Oh C, Baco M, Amin-Mansour A, Rabasha B, Bahl S, Mullane S, Robinson B, Aldubayan S, Khani F, Karir B, Kim E, Chimene-Weiss J, Hofree M, Romanel A, Osborne J, Kim J, Azabdaftari G, Woloszynska-Read A, Sfanos K, De Marzo A, Demichelis F, Gabriel S, Van Allen E, Mesirov J, Tamayo P, Rubin M, Powell I, Garraway L. Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations. Cancer Discovery 2017, 7: 973-983. PMID: 28515055, PMCID: PMC5836784, DOI: 10.1158/2159-8290.cd-16-0960.Peer-Reviewed Original ResearchConceptsProstate cancerRecurrent loss-of-function mutationsSystematic genome sequencingCastration-resistant prostate cancerLethal castration-resistant prostate cancerProstate cancer tumor suppressor geneCancer sequencing studiesCancer genome characterizationLoss-of-function mutationsIncreased anchorage-independent growthPrimary prostate cancerAfrican American menProstate cancer cohortAnchorage-independent growthTumor suppressor geneProstate cancer genesGene expression signaturesTranscriptional repressorGenomic characterizationSequencing studiesExome sequencingCancer genesAndrogen signalingGene mutationsCancer cohort
2016
Characterizing genomic alterations in cancer by complementary functional associations
Kim J, Botvinnik O, Abudayyeh O, Birger C, Rosenbluh J, Shrestha Y, Abazeed M, Hammerman P, DiCara D, Konieczkowski D, Johannessen C, Liberzon A, Alizad-Rahvar A, Alexe G, Aguirre A, Ghandi M, Greulich H, Vazquez F, Weir B, Van Allen E, Tsherniak A, Shao D, Zack T, Noble M, Getz G, Beroukhim R, Garraway L, Ardakani M, Romualdi C, Sales G, Barbie D, Boehm J, Hahn W, Mesirov J, Tamayo P. Characterizing genomic alterations in cancer by complementary functional associations. Nature Biotechnology 2016, 34: 539-546. PMID: 27088724, PMCID: PMC4868596, DOI: 10.1038/nbt.3527.Peer-Reviewed Original Research
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-grade