2024
Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer
Robles-Oteíza C, Hastings K, Choi J, Sirois I, Ravi A, Expósito F, de Miguel F, Knight J, López-Giráldez F, Choi H, Socci N, Merghoub T, Awad M, Getz G, Gainor J, Hellmann M, Caron É, Kaech S, Politi K. Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer. Journal Of Experimental Medicine 2024, 222: e20231106. PMID: 39585348, DOI: 10.1084/jem.20231106.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsNon-small cell lung cancerAcquired resistanceCheckpoint inhibitorsResistant tumorsPatients treated with anti-PD-1/PD-L1 therapyAnti-PD-1/PD-L1 therapyLung cancerResistance to immune checkpoint inhibitorsAssociated with decreased progression-free survivalHypoxia activated pro-drugsTargeting hypoxic tumor regionsTreat non-small cell lung cancerAnti-CTLA-4Anti-PD-1Immune checkpoint inhibitionTumor metabolic featuresProgression-free survivalCell lung cancerResistant cancer cellsHypoxic tumor regionsMHC-II levelsRegions of hypoxiaKnock-outCheckpoint inhibition
2023
PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells.
Exposito F, Redrado M, Houry M, Hastings K, Molero-Abraham M, Lozano T, Solorzano J, Sanz-Ortega J, Adradas V, Amat R, Redin E, Leon S, Legarra N, Garcia J, Serrano D, Valencia K, Robles-Oteiza C, Foggetti G, Otegui N, Felip E, Lasarte J, Paz-Ares L, Zugazagoitia J, Politi K, Montuenga L, Calvo A. PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells. Cancer Research 2023, 83: 2513-2526. PMID: 37311042, DOI: 10.1158/0008-5472.can-22-3023.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerLung squamous carcinomaAnti-PD-1 therapyRegulatory T cellsCell lung cancerImmunosuppressive microenvironmentLung cancerImmunotherapy resistanceT cellsWorse progression-free survivalCell death protein 1PTEN lossAnti-TGFβ antibodyConversion of CD4PI3K/AKT/mTOR pathwayProgression-free survivalDeath protein 1Treatment of miceImmunosuppressive tumor microenvironmentPTEN/PI3K/AKT/mTOR pathwayAKT/mTOR pathwayPD-L1TLR agonistsTumor rejectionSquamous carcinoma
2022
Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer
Adua S, Arnal-Estapé A, Zhao M, Qi B, Liu Z, Kravitz C, Hulme H, Strittmatter N, López-Giráldez F, Chande S, Albert A, Melnick M, Hu B, Politi K, Chiang V, Colclough N, Goodwin R, Cross D, Smith P, Nguyen D. Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer. Nature Communications 2022, 13: 7690. PMID: 36509758, PMCID: PMC9744876, DOI: 10.1038/s41467-022-34889-z.Peer-Reviewed Original ResearchConceptsGene expression programsRas homolog family member ACancer cellsFamily member AEpidermal growth factor receptorExpression programsMetastatic cancer cellsSRF signalingGrowth factor receptorTumor microenvironmentLung cancerFunctional linkExtracellular lamininDrug-resistant cancer cellsMutant non-small cell lung cancerNon-small cell lung cancerCentral nervous system relapseMolecular studiesMember AEGFR-mutant lung cancerFactor receptorNervous system relapseCell lung cancerDisseminated tumor cellsBrain tumor microenvironment
2012
Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response
Sangodkar J, Dhawan N, Melville H, Singh V, Yuan E, Rana H, Izadmehr S, Farrington C, Mazhar S, Katz S, Albano T, Arnovitz P, Okrent R, Ohlmeyer M, Galsky M, Burstein D, Zhang D, Politi K, DiFeo A, Narla G. Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response. Journal Of Clinical Investigation 2012, 122: 2637-2651. PMID: 22653055, PMCID: PMC3386822, DOI: 10.1172/jci62058.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAdenocarcinomaAdenocarcinoma of LungAnimalsAntineoplastic AgentsCell Line, TumorDrug Resistance, NeoplasmDrug SynergismEnzyme ActivationErbB ReceptorsErlotinib HydrochlorideFemaleForkhead Box Protein O1Forkhead Transcription FactorsGene Expression Regulation, NeoplasticHumansKruppel-Like Factor 6Kruppel-Like Transcription FactorsLung NeoplasmsMiceMice, Inbred BALB CMice, NudeMutationProto-Oncogene ProteinsProto-Oncogene Proteins c-aktQuinazolinesReal-Time Polymerase Chain ReactionSignal TransductionTranscription, GeneticTrifluoperazineTumor BurdenXenograft Model Antitumor AssaysConceptsAnti-EGFR-based therapyEGFR signalingKruppel-like factor 6Lung adenocarcinomaForkhead box O1Xenograft models of lung adenocarcinomaModel of lung adenocarcinomaMetastatic lung adenocarcinomaTreat advanced cancersMolecular drivers of disease progressionDrivers of disease progressionOncogenic EGFR signalingActivation of Akt signalingFoxO1 nuclear exportTreating resistant diseaseIn vivo modelsCell culturesErlotinib resistanceResistant diseaseTreatment responseMolecular therapiesXenograft modelFDA-approved drugsDisease progressionEGFR activation
2005
Oncogenes Come of Age
VARMUS H, PAO W, POLITI K, PODSYPANINA K, DU Y. Oncogenes Come of Age. Cold Spring Harbor Symposia On Quantitative Biology 2005, 70: 1-9. PMID: 16869733, PMCID: PMC1791364, DOI: 10.1101/sqb.2005.70.039.Chapters