Zachary Yochum, MD, PhD
Clinical FellowAbout
Research
Publications
Featured Publications
Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer
Yochum Z, Cades J, Wang H, Chatterjee S, Simons B, O’Brien J, Khetarpal S, Lemtiri-Chlieh G, Myers K, Huang E, Rudin C, Tran P, Burns T. Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene 2018, 38: 656-670. PMID: 30171258, PMCID: PMC6358506, DOI: 10.1038/s41388-018-0482-y.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAmino Acid SubstitutionAniline CompoundsCarcinoma, Non-Small-Cell LungCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionErbB ReceptorsHEK293 CellsHumansLung NeoplasmsMutation, MissenseNeoplasm ProteinsNuclear ProteinsPiperazinesProtein Kinase InhibitorsTwist-Related Protein 1ConceptsEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitorsEGFR-TKI resistanceGeneration EGFR tyrosine kinase inhibitorsCell lung cancerEGFR-mutant NSCLCLung cancerTKI resistanceTwist1 overexpressionFirst-generation EGFR tyrosine kinase inhibitorsThird-generation EGFR tyrosine kinase inhibitorEGFR-mutant lung cancerEGFR-mutant NSCLC cellsFirst-line settingLong-term efficacyDe novo resistanceT790M mutationErlotinib-induced apoptosisEpithelial-mesenchymal transition transcription factorsDrivers of EMTDrivers of resistanceEMT transcription factor TWIST1Osimertinib resistanceErlotinib resistanceNovo resistanceTWIST1 regulation of circRNA: a novel mechanism to promote epithelial-mesenchymal transition in hepatocellular carcinoma
Yochum Z, Burns T. TWIST1 regulation of circRNA: a novel mechanism to promote epithelial-mesenchymal transition in hepatocellular carcinoma. Non-coding RNA Investigation 2018, 2: 71-71. PMID: 30734026, PMCID: PMC6363344, DOI: 10.21037/ncri.2018.12.01.Peer-Reviewed Original ResearchEpithelial-mesenchymal transitionCell-extracellular matrix interactionsApical-basal polarityCell-cell interactionsEpithelial cellsGenetic changesMesenchymal morphologyMatrix interactionsNovel mechanismProtein 1E-cadherinFibroblast-specific protein-1GenesCellsCircRNAsRegulationUpregulationInteractionVimentinHormone gene signature guides a novel therapeutic opportunity to improve sensitivity to HER family inhibition in lung cancer
Yochum Z, Stabile L. Hormone gene signature guides a novel therapeutic opportunity to improve sensitivity to HER family inhibition in lung cancer. Translational Lung Cancer Research 2020, 9: 1599-1605. PMID: 32953532, PMCID: PMC7481617, DOI: 10.21037/tlcr-20-617.Peer-Reviewed Original ResearchAlternative splicing of HER2: a novel mediator of EGFR TKI resistance
Yochum Z, Villaruz L. Alternative splicing of HER2: a novel mediator of EGFR TKI resistance. Translational Lung Cancer Research 2020, 9: 1606-1612. PMID: 32953533, PMCID: PMC7481647, DOI: 10.21037/tlcr-20-618.Peer-Reviewed Original ResearchParadoxical functions of ZEB1 in EGFR -mutant lung cancer: tumor suppressor and driver of therapeutic resistance
Yochum Z, Socinski M, Burns T. Paradoxical functions of ZEB1 in EGFR -mutant lung cancer: tumor suppressor and driver of therapeutic resistance. Journal Of Thoracic Disease 2016, 8: e1528-e1531. PMID: 28066651, PMCID: PMC5179406, DOI: 10.21037/jtd.2016.11.59.Peer-Reviewed Original ResearchNon-small cell lung cancerLung cancerEGFR-mutant lung cancerCell lung cancerCancer-related deathAmplification/mutationEGFR mutationsALK translocationKRAS mutationsDistinct subtypesTherapeutic resistanceCancerMolecular driversPatientsTumor suppressorParadoxical functionsMutationsSubtypesSignificant advancesZEB1A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer
Yochum Z, Cades J, Mazzacurati L, Neumann N, Khetarpal S, Chatterjee S, Wang H, Attar M, Huang E, Chatley S, Nugent K, Somasundaram A, Engh J, Ewald A, Cho Y, Rudin C, Tran P, Burns T. A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer. Molecular Cancer Research 2017, 15: 1764-1776. PMID: 28851812, PMCID: PMC5712248, DOI: 10.1158/1541-7786.mcr-17-0298.Peer-Reviewed Original ResearchConceptsOncogene-driven NSCLCTwist1 functionPatient-derived xenograft mouse modelsMarked anti-tumor activityEpithelial-mesenchymal transition transcription factorsNon-small cell lung cancer tumorigenesisSolid tumor malignanciesSingle-cell disseminationLung cancer tumorigenesisNovel therapeutic strategiesXenograft mouse modelCell lung cancer tumorigenesisEffects of harmineAnti-tumor activityConnectivity mapping analysisE2A proteinsNSCLC cellsNSCLC tumorigenesisMutant NSCLCAnalogs/derivativesMouse modelTherapeutic strategiesHarmine treatmentDimer partnerTherapeutic targetTMEM16A/ANO1 Inhibits Apoptosis Via Downregulation of Bim Expression
Godse N, Khan N, Yochum Z, Gomez-Casal R, Kemp C, Shiwarski D, Seethala R, Kulich S, Seshadri M, Burns T, Duvvuri U. TMEM16A/ANO1 Inhibits Apoptosis Via Downregulation of Bim Expression. Clinical Cancer Research 2017, 23: 7324-7332. PMID: 28899969, PMCID: PMC5898434, DOI: 10.1158/1078-0432.ccr-17-1561.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaGreater tumor sizeSquamous cell carcinomaCalcium-activated chloride channelClin Cancer ResERK 1/2 activityVariety of cancersTMEM16A overexpressionCisplatin-resistant phenotypeAggressive diseaseTumor sizeCell carcinomaHuman HNSCCLaryngeal cancerHNSCC samplesTMEM16A expressionChemoradiation failureAnti-apoptotic roleOverexpression rateTranslational investigationsMalignant cellsPotential biomarkersSimilar outcomesCancer ResProtein expressionP190B RhoGAP Regulates Chromosome Segregation in Cancer Cells
Hwang M, Peddibhotla S, McHenry P, Chang P, Yochum Z, Park K, Sears J, Vargo-Gogola T. P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells. Cancers 2012, 4: 475-489. PMID: 22582143, PMCID: PMC3348653, DOI: 10.3390/cancers4020475.Peer-Reviewed Original ResearchChromosome segregationMicrotubule-kinetochore attachmentsDisruption of mitosisRegulator of mitosisDeficient MCF-7 cellsP190B Rho GTPaseCancer cellsMitotic defectsRho proteinsRho GTPasesRac GTPaseRho GTPaseRac activityKnockdown cellsCell cycle analysisDeficient cellsChemical inhibitionNovel roleMitosisP190BS transitionS phaseHeLa cellsAltered expressionMCF-7 cellsRechallenging with anti-PD-1 therapy in advanced renal cell carcinoma
Yochum Z, Braun D. Rechallenging with anti-PD-1 therapy in advanced renal cell carcinoma. The Lancet 2024, 404: 1280-1282. PMID: 39284326, DOI: 10.1016/s0140-6736(24)01866-x.Peer-Reviewed Original ResearchTWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer
Kumar V, Yochum Z, Devadassan P, Huang E, Miller E, Baruwal R, Rumde P, GaitherDavis A, Stabile L, Burns T. TWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer. Oncogene 2024, 43: 1431-1444. PMID: 38485737, PMCID: PMC11068584, DOI: 10.1038/s41388-024-02987-5.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsTKI resistanceMET amplificationEpithelial-mesenchymal transitionMET tyrosine kinase inhibitorsOvercome resistanceTyrosine kinase inhibitor resistanceTargetable oncogenic driversResistance in vitroEffective therapeutic strategySuppression of p27Inhibition of Twist1MET alterationsPDX modelsMET pathwayHGF/MET pathwayOncogenic driversLung cancerLung tumorigenesisKinase inhibitorsP27 expressionTherapeutic strategiesPharmacological inhibitionDownstream mediatorTwist1