Anna Wurtz
Research Associate Yale Cancer CenterCards
About
Research
Publications
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
Co-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer
Stockhammer P, Grant M, Wurtz A, Foggetti G, Expósito F, Gu J, Zhao H, Choi J, Chung S, Li F, Walther Z, Dietz J, Duffield E, Gettinger S, Politi K, Goldberg S. Co-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer. Journal Of Thoracic Oncology 2023, 19: 240-251. PMID: 37806385, PMCID: PMC11364167, DOI: 10.1016/j.jtho.2023.10.001.Peer-Reviewed Original ResearchProgression-free survivalEGFR-mutant NSCLCTP53 mutationsOverall survivalClinical outcomesEGFR-TKIInferior outcomesWorse outcomesYale cohortMetastatic EGFR-mutant NSCLCShorter progression-free survivalEGFR-mutant lung cancerTyrosine kinase inhibitor therapyFirst-line TKIYale Cancer CenterSecond-line therapyInferior clinical outcomesSubset of patientsKinase inhibitor therapyAdditional therapeutic interventionsAggressive disease phenotypeCo-occurring alterationsTumor suppressor gene alterationsTumor genomic profilingMultiple tumor suppressor genesMammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
de Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, PMCID: PMC10957226, DOI: 10.1016/j.ccell.2023.07.005.Peer-Reviewed Original ResearchConceptsMammalian SWI/SNF chromatinSWI/SNF chromatinMSWI/SNF complexesGenome-wide localizationGene regulatory signaturesNon-genetic mechanismsEpithelial cell differentiationEGFR-mutant cellsChromatin accessibilitySNF complexCellular programsRegulatory signaturesTKI-resistant lung cancerGene targetsKinase inhibitor resistanceCell differentiationMesenchymal transitionTKI resistancePharmacologic disruptionTyrosine kinase inhibitor resistanceCell proliferationChromatinInhibitor resistanceEGFR-mutant lungKinase inhibitorsEfficacy 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
2021
Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma
Foggetti G, Li C, Cai H, Hellyer JA, Lin WY, Ayeni D, Hastings K, Choi J, Wurtz A, Andrejka L, Maghini DG, Rashleigh N, Levy S, Homer R, Gettinger SN, Diehn M, Wakelee HA, Petrov DA, Winslow MM, Politi K. Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma. Cancer Discovery 2021, 11: 1736-1753. PMID: 33707235, PMCID: PMC8530463, DOI: 10.1158/2159-8290.cd-20-1385.Peer-Reviewed Original ResearchConceptsSuppressor geneKey tumor suppressorPutative tumor suppressor geneTumor suppressor geneSensitivity of EGFRTumor growthOncogenic contextTumor suppressorHuman EGFRGenetic determinantsKeap1 pathwayComplex genotypesTumor suppressor gene alterationsLung cancer growthGenesDeficient lung adenocarcinomaLung adenocarcinomaGenetic alterationsIssue featureStrong driverCancer growthEGFR inhibitorsKinase inhibitorsInactivationGene alterations
2019
The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma
Truini A, Starrett JH, Stewart T, Ashtekar K, Walther Z, Wurtz A, Lu D, Park JH, DeVeaux M, Song X, Gettinger S, Zelterman D, Lemmon MA, Goldberg SB, Politi K. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clinical Cancer Research 2019, 25: 6382-6391. PMID: 31182434, PMCID: PMC6825535, DOI: 10.1158/1078-0432.ccr-19-0780.Peer-Reviewed Original ResearchEGFR 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 outcomesOutcomes of EGFR-mutant lung adenocarcinomas (AC) that transform to small cell lung cancer (SCLC).
Marcoux N, Gettinger S, O'Kane G, Arbour K, Neal J, Husain H, Evans T, Brahmer J, Muzikansky A, Bonomi P, Del Prete S, Wurtz A, Farago A, Dias-Santagata D, Mino-Kenudson M, Yu H, Wakelee H, Shepherd F, Piotrowska Z, Sequist L. Outcomes of EGFR-mutant lung adenocarcinomas (AC) that transform to small cell lung cancer (SCLC). Journal Of Clinical Oncology 2018, 36: 8573-8573. DOI: 10.1200/jco.2018.36.15_suppl.8573.Peer-Reviewed Original ResearchClinical 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
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