2023
Platinum Sensitivity in IDH1/2 Mutated Intrahepatic Cholangiocarcinoma: Not All “BRCAness” Is Created Equal
Doroshow D, Wei W, Mehrotra M, Sia D, Eder J, Bindra R, Houldsworth J, LoRusso P, Walther Z. Platinum Sensitivity in IDH1/2 Mutated Intrahepatic Cholangiocarcinoma: Not All “BRCAness” Is Created Equal. Cancer Investigation 2023, 41: 646-655. PMID: 37505929, DOI: 10.1080/07357907.2023.2242957.Peer-Reviewed Original ResearchConceptsClinical benefit rateIntrahepatic cholangiocarcinomaPlatinum sensitivityUnresectable intrahepatic cholangiocarcinomaObjective response rateMulticenter retrospective studyHomologous recombination repairDefective homologous recombination (HR) repairPrimary endpointPlatinum chemotherapyRetrospective studyPreclinical dataBenefit rateWildtype tumorsResponse rateMT tumorsWT diseasePatientsGene defectsCholangiocarcinomaTumorsEfficacy 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
2022
Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations
van Alderwerelt van Rosenburgh I, Lu D, Grant M, Stayrook S, Phadke M, Walther Z, Goldberg S, Politi K, Lemmon M, Ashtekar K, Tsutsui Y. Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations. Nature Communications 2022, 13: 6791. PMID: 36357385, PMCID: PMC9649653, DOI: 10.1038/s41467-022-34398-z.Peer-Reviewed Original ResearchCirculating Tumor DNA Kinetics Predict Progression-Free and Overall Survival in EGFR TKI–Treated Patients with EGFR-Mutant NSCLC (SWOG S1403)
Mack PC, Miao J, Redman MW, Moon J, Goldberg SB, Herbst RS, Melnick MA, Walther Z, Hirsch FR, Politi K, Kelly K, Gandara DR. Circulating Tumor DNA Kinetics Predict Progression-Free and Overall Survival in EGFR TKI–Treated Patients with EGFR-Mutant NSCLC (SWOG S1403). Clinical Cancer Research 2022, 28: 3752-3760. PMID: 35713632, PMCID: PMC9444942, DOI: 10.1158/1078-0432.ccr-22-0741.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalEGFR mutationsNon-small cell lung cancerCycle 3 day 1Median progression-free survivalMedian overall survivalRisk of progressionCell lung cancerPresence of brainEGFR-mutant NSCLCBaseline ctDNAM1b stageProgression-FreeRECIST responseSerial plasmaLiver metastasesDecreased riskEGFR-TKILung cancerComplete clearanceLong-term benefitsClinical trialsTreatment outcomesPlasma clearance
2021
Epidermotropic metastasis of squamous cell carcinoma of the tonsil: A case report with molecular confirmation
Li P, Barbieri A, Walther Z, McNiff J, Panse G. Epidermotropic metastasis of squamous cell carcinoma of the tonsil: A case report with molecular confirmation. Journal Of Cutaneous Pathology 2021, 48: 1514-1519. PMID: 34302376, DOI: 10.1111/cup.14108.Peer-Reviewed Case Reports and Technical NotesConceptsSquamous cell carcinomaOropharyngeal squamous cell carcinomaCell carcinomaDe novo squamous cell carcinomaPrimary oropharyngeal squamous cell carcinomaTonsillar squamous cell carcinomaTargetable genetic aberrationsLesion biopsy specimensSkin biopsy specimenSkin lesion biopsy specimensMetastatic diseaseEpidermal involvementEpidermotropic metastasesMetastatic lesionsPoor prognosisBiopsy specimenCase reportClinical historyBiopsy specimensSecondary diseaseSkin lesionsTumor originMetastatic specimensMetastasisNeck skinYale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan
Gibson JA, Finberg KE, Nalbantoglu I, Cecchini M, Ganzak A, Walther Z, Sklar JL, Eder JP, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan. The Lancet Oncology 2021, 22: 306-307. PMID: 33662283, DOI: 10.1016/s1470-2045(20)30683-5.Peer-Reviewed Case Reports and Technical Notes
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 Research
2018
Yale Cancer Center Precision Medicine Tumor Board: two patients, one targeted therapy, different outcomes
Cecchini M, Walther Z, Sklar JL, Bindra RS, Petrylak DP, Eder JP, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: two patients, one targeted therapy, different outcomes. The Lancet Oncology 2018, 19: 23-24. PMID: 29304353, DOI: 10.1016/s1470-2045(17)30916-6.Peer-Reviewed Case Reports and Technical Notes
2014
Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1
Pirazzoli V, Nebhan C, Song X, Wurtz A, Walther Z, Cai G, Zhao Z, Jia P, de Stanchina E, Shapiro EM, Gale M, Yin R, Horn L, Carbone DP, Stephens PJ, Miller V, Gettinger S, Pao W, Politi K. Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1. Cell Reports 2014, 7: 999-1008. PMID: 24813888, PMCID: PMC4074596, DOI: 10.1016/j.celrep.2014.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAfatinibAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCetuximabDrug Resistance, NeoplasmErbB ReceptorsHumansLung NeoplasmsMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesMutationQuinazolinesRandom AllocationTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsTyrosine kinase inhibitorsFirst-generation tyrosine kinase inhibitorEGFR-mutant lung adenocarcinomaLung adenocarcinomaMechanisms of resistanceEGFR antibody cetuximabPotential therapeutic strategyBiopsy specimensAntibody cetuximabDrug combinationsMouse modelTherapeutic strategiesAfatinibAddition of rapamycinCetuximabDual inhibitionAcquired ResistanceKinase inhibitorsGenomic alterationsAdenocarcinomaPatientsActivationGenomic mechanismsDrugsMTORC1 activation
2008
A PDZ‐Binding Motif Controls Basolateral Targeting of Syndecan‐1 Along the Biosynthetic Pathway in Polarized Epithelial Cells
Maday S, Anderson E, Chang HC, Shorter J, Satoh A, Sfakianos J, Fölsch H, Anderson JM, Walther Z, Mellman I. A PDZ‐Binding Motif Controls Basolateral Targeting of Syndecan‐1 Along the Biosynthetic Pathway in Polarized Epithelial Cells. Traffic 2008, 9: 1915-1924. PMID: 18764819, PMCID: PMC2820280, DOI: 10.1111/j.1600-0854.2008.00805.x.Peer-Reviewed Original ResearchConceptsPolarized epithelial cellsBiosynthetic pathwayPDZ domain-containing proteinsType II PDZDomain-containing proteinsPDZ-Binding MotifSyndecan-1Cell surface proteoglycansEpithelial cellsBasolateral targetingNormal epithelial morphologyBasolateral domainMotif leadPlasma membranePDZBasolateral localizationSurface proteoglycansBasolateral surfaceApical surfaceEpithelial morphologyMotifPotential rolePathwayCellsMislocalization
1996
The kinesin-homologous protein encoded by the Chlamydomonas FLA10 gene is associated with basal bodies and centrioles
Vashishtha M, Walther Z, Hall J. The kinesin-homologous protein encoded by the Chlamydomonas FLA10 gene is associated with basal bodies and centrioles. Journal Of Cell Science 1996, 109: 541-549. PMID: 8907700, DOI: 10.1242/jcs.109.3.541.Peer-Reviewed Original ResearchConceptsBasal bodiesMitotic spindleHomologous proteinsCell cycleUni linkage groupFamily of proteinsMotor domainCarboxy-terminal thirdTemperature-sensitive defectKinesin-related proteinEukaryotic evolutionFlagellar assemblyFlagellar developmentLinkage groupsFlagellar componentsSubcellular localizationPunctate structuresSea urchinsMolecular defectsProteinCentriolesAnalogous roleDirect roleMitosisGenes
1988
slit: An EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system
Rothberg J, Hartley D, Walther Z, Artavanis-Tsakonas S. slit: An EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system. Cell 1988, 55: 1047-1059. PMID: 3144436, DOI: 10.1016/0092-8674(88)90249-8.Peer-Reviewed Original ResearchConceptsEmbryonic central nervous systemD. melanogasterDeduced protein sequenceCentral nervous systemMidline glial cellsLongitudinal axon tractsEGF-like repeatsHigh-level expressionMolecular dataNervous systemProtein sequencesLoci resultsFamily of lociExtracellular localizationLevel expressionLociMelanogasterSitu hybridizationAxon tractsGenesEmbryosGlial cellsAntibody stainingPossible roleSequence