2024
ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.
Hu B, Wiesehöfer M, de Miguel F, Liu Z, Chan L, Choi J, Melnick M, Arnal Estape A, Walther Z, Zhao D, Lopez-Giraldez F, Wurtz A, Cai G, Fan R, Gettinger S, Xiao A, Yan Q, Homer R, Nguyen D, Politi K. ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts. Cancer Research 2024, 84: 1303-1319. PMID: 38359163, PMCID: PMC11142404, DOI: 10.1158/0008-5472.can-23-0438.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsPatient-derived xenograftsEGFR mutant lung cancerMutant lung cancerPre-treatment tumorsResidual diseaseDrug toleranceLung cancerResidual tumor cells in vivoEGFR mutant lung adenocarcinomaTyrosine kinase inhibitor osimertinibEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitor treatmentTumor cells in vivoMutant lung adenocarcinomaMaximal tumor regressionTranscription factor Ascl1Drug-tolerant cellsTime of maximal responseEvidence of cellsCells in vivoOsimertinib treatmentTumor regressionSingle cell transcriptional profilingTumor cells
2023
Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations
Grant M, Aredo J, Starrett J, Stockhammer P, van Rosenburgh I, Wurtz A, Piper-Valillo A, Piotrowska Z, Falcon C, Yu H, Aggarwal C, Scholes D, Patil T, Nguyen C, Phadke M, Li F, Neal J, Lemmon M, Walther Z, Politi K, Goldberg S. Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations. Clinical Cancer Research 2023, 29: of1-of8. PMID: 36913537, PMCID: PMC10493186, DOI: 10.1158/1078-0432.ccr-22-3497.Peer-Reviewed Original ResearchConceptsProgression-free survivalNon-small cell lung cancerInferior progression-free survivalMulticenter retrospective cohortEfficacy of osimertinibMulti-institutional cohortCell lung cancerExon 19 deletion mutationUncommon EGFRRetrospective cohortClinical outcomesClinical efficacyLung cancerOsimertinib efficacyEGFR mutationsPreclinical modelsEx19delPatientsAACR Genie databaseLater linesOsimertinibMutant cohortFirst lineCohortEfficacy
2019
EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer
Hastings K, Yu HA, Wei W, Sanchez-Vega F, DeVeaux M, Choi J, Rizvi H, Lisberg A, Truini A, Lydon CA, Liu Z, Henick BS, Wurtz A, Cai G, Plodkowski AJ, Long NM, Halpenny DF, Killam J, Oliva I, Schultz N, Riely GJ, Arcila ME, Ladanyi M, Zelterman D, Herbst RS, Goldberg SB, Awad MM, Garon EB, Gettinger S, Hellmann MD, Politi K. EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer. Annals Of Oncology 2019, 30: 1311-1320. PMID: 31086949, PMCID: PMC6683857, DOI: 10.1093/annonc/mdz141.Peer-Reviewed Original ResearchMeSH KeywordsAgedAllelesAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmErbB ReceptorsFemaleGenetic HeterogeneityHumansLungLung NeoplasmsMaleMiddle AgedMutationProgrammed Cell Death 1 ReceptorProgression-Free SurvivalRetrospective StudiesTobacco SmokingConceptsEGFR-mutant tumorsMemorial Sloan-Kettering Cancer CenterYale Cancer CenterImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint blockadeTumor mutation burdenCancer CenterLung tumorsCheckpoint blockadeEGFR mutant lung tumorsMutant tumorsCheckpoint inhibitorsLung cancerMutation burdenImmune checkpoint blockade treatmentLow tumor mutation burdenDana-Farber Cancer InstituteEGFR wild-type lung cancersCheckpoint blockade treatmentCell lung cancerEGFR mutation subtypesSimilar smoking historyCell death 1Lung cancer cases
2018
EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes
Marcoux N, Gettinger SN, O’Kane G, Arbour KC, Neal JW, Husain H, Evans TL, Brahmer JR, Muzikansky A, Bonomi PD, del Prete S, Wurtz A, Farago AF, Dias-Santagata D, Mino-Kenudson M, Reckamp KL, Yu HA, Wakelee HA, Shepherd FA, Piotrowska Z, Sequist LV. EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. Journal Of Clinical Oncology 2018, 37: 278-285. PMID: 30550363, PMCID: PMC7001776, DOI: 10.1200/jco.18.01585.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Non-Small-Cell LungClass I Phosphatidylinositol 3-KinasesErbB ReceptorsFemaleGenetic Predisposition to DiseaseHumansLung NeoplasmsMaleMiddle AgedMutationNeoplasm GradingNorth AmericaPhenotypeRetinoblastoma Binding ProteinsRetrospective StudiesSmall Cell Lung CarcinomaTime FactorsTreatment OutcomeTumor Suppressor Protein p53Ubiquitin-Protein LigasesConceptsNon-small cell lung cancerSmall cell lung cancerEGFR-mutant non-small cell lung cancerSCLC transformationLung cancerNeuroendocrine carcinomaEGFR mutationsDe novo small cell lung cancersInitial lung cancer diagnosisHigh-grade neuroendocrine carcinomaEGFR tyrosine kinase inhibitorsT790M positivityMedian overall survivalCell lung cancerTyrosine kinase inhibitorsHigh response rateEGFR-mutant adenocarcinomaLung cancer diagnosisCNS metastasesCheckpoint inhibitorsMedian survivalOverall survivalClinical courseMixed histologyClinical outcomesClinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non–Small Cell Lung Cancer
Gettinger SN, Wurtz A, Goldberg SB, Rimm D, Schalper K, Kaech S, Kavathas P, Chiang A, Lilenbaum R, Zelterman D, Politi K, Herbst R. Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2018, 13: 831-839. PMID: 29578107, PMCID: PMC6485248, DOI: 10.1016/j.jtho.2018.03.008.Peer-Reviewed Original ResearchConceptsPD-1 axis inhibitorsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerInhibitor therapyLocal therapyLymph nodesLung cancerSurvival rateSolid Tumors v1.1Response Evaluation CriteriaSite of diseaseProgression of diseaseProgressive diseaseClinical patternLN metastasisSuch patientsClinical featuresMedian timeRadiographic featuresTumor regressionProlonged benefitPatientsTherapyResponse criteria
2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutations
2014
Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer
de Bruin EC, Cowell C, Warne PH, Jiang M, Saunders RE, Melnick MA, Gettinger S, Walther Z, Wurtz A, Heynen GJ, Heideman DA, Gómez-Román J, García-Castaño A, Gong Y, Ladanyi M, Varmus H, Bernards R, Smit EF, Politi K, Downward J. Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer. Cancer Discovery 2014, 4: 606-619. PMID: 24535670, PMCID: PMC4011693, DOI: 10.1158/2159-8290.cd-13-0741.Peer-Reviewed Original ResearchConceptsLung cancerMAP-ERK kinase (MEK) inhibitorsEGF receptorEGFR-mutant lung adenocarcinomaKinase inhibitorsHuman lung cancer cell linesResistance of lungSubgroup of patientsLung cancer cell linesCancer cell linesClinical responsivenessCombination therapyEGFR-TKIEGFR mutationsErlotinib resistanceLung adenocarcinomaRAS-ERK signalingEGFR inhibitionMEK inhibitorsErlotinibReduced expressionNF1 expressionPatientsCell linesNeurofibromin levels