Zenta Walther, MD, PhD
Associate Professor of PathologyCards
About
Research
Publications
2025
A Concordance Study Among 26 NGS Laboratories Participating in the National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) Clinical Trial.
Zane L, Yee L, Chang T, Sklar J, Yang G, Wen J, Li P, Harrington R, Sims D, Harper K, Trent J, LoBello J, Szelinger S, Benson K, Zeng J, Poorman K, Xu D, Frampton G, Pavlick D, Miller V, Tandon B, Swat W, Weiss L, Funari V, Conroy J, Prescott J, Chandra P, Ma C, Champion K, Baschkopf G, Fesko Y, Freitas T, Tomlins S, Hovelson D, White K, Sorrells S, Tell R, Beaubier N, King D, Li L, Kelly K, Uvalic J, Meyers B, Kolhe R, Lindeman N, Baltay M, Sholl L, Lopategui J, Vail E, Zhang W, Telatar M, Afkhami M, Hsiao S, Mansukhani M, Adams E, Jiang L, Aldape K, Raffeld M, Xi L, Stehr H, Segal J, Aisner D, Davies K, Brown N, Livingston R, Konnick E, Song W, Solomon J, Walther Z, McShane L, Harris L, Chen A, Tsongalis G, Hamilton S, Flaherty K, O'Dwyer P, Conley B, Patton D, Iafrate A, Williams P, Tricoli J, Karlovich C. A Concordance Study Among 26 NGS Laboratories Participating in the National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) Clinical Trial. Clinical Cancer Research 2025 PMID: 40465838, DOI: 10.1158/1078-0432.ccr-24-2188.Peer-Reviewed Original ResearchVariant detectionVariant reportingEstimates of copy numberTarget enrichment methodLow-complexity regionsCentral laboratoryNational Cancer Institute-Molecular AnalysisNCI-MATCH trialVariant interpretationVariant classesCopy numberBioinformatics analysisCNV reporterNGS assayCLIA-certified laboratoryEnrichment methodNGSHybridization captureIndelsNCI-MATCHTumor profiling testsCell linesTherapy choiceClinical samplesSNVsHeterogeneous Tumor Profiles in Hepatocellular Carcinoma: An Example of Late Recurrences With Genetically Distinct Tumors Over a 10-Year Survival
Cao Y, Laurans M, Onyiuke I, Walther Z, Zhang X, Rose M, Taddei T. Heterogeneous Tumor Profiles in Hepatocellular Carcinoma: An Example of Late Recurrences With Genetically Distinct Tumors Over a 10-Year Survival. ACG Case Reports Journal 2025, 12: e01670. DOI: 10.14309/crj.0000000000001670.Peer-Reviewed Original ResearchHepatocellular carcinomaTumor profilingLate recurrenceNext-generation sequencingRuptured hepatocellular carcinomaMetastasis 3 yearsDistinct tumorsProlonged survivalGenetically distinct tumorsRecurrenceUnique caseTargeted mutationCarcinomaTumorClinical insightsSurvivalPresentationGenetic sequencesPatients110 Characterization of Frequency and Spectrum of PIK3CA Somatic Mutations in Advanced Breast Cancer
Amraei R, Kahn A, Walther Z, Finberg K, Gibson J, Kahila M. 110 Characterization of Frequency and Spectrum of PIK3CA Somatic Mutations in Advanced Breast Cancer. Laboratory Investigation 2025, 105: 102334. DOI: 10.1016/j.labinv.2024.102334.Peer-Reviewed Original ResearchAuthor Correction: CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors
Skoulidis F, Araujo H, Do M, Qian Y, Sun X, Cobo A, Le J, Montesion M, Palmer R, Jahchan N, Juan J, Min C, Yu Y, Pan X, Arbour K, Vokes N, Schmidt S, Molkentine D, Owen D, Memmott R, Patil P, Marmarelis M, Awad M, Murray J, Hellyer J, Gainor J, Dimou A, Bestvina C, Shu C, Riess J, Blakely C, Pecot C, Mezquita L, Tabbó F, Scheffler M, Digumarthy S, Mooradian M, Sacher A, Lau S, Saltos A, Rotow J, Johnson R, Liu C, Stewart T, Goldberg S, Killam J, Walther Z, Schalper K, Davies K, Woodcock M, Anagnostou V, Marrone K, Forde P, Ricciuti B, Venkatraman D, Van Allen E, Cummings A, Goldman J, Shaish H, Kier M, Katz S, Aggarwal C, Ni Y, Azok J, Segal J, Ritterhouse L, Neal J, Lacroix L, Elamin Y, Negrao M, Le X, Lam V, Lewis W, Kemp H, Carter B, Roth J, Swisher S, Lee R, Zhou T, Poteete A, Kong Y, Takehara T, Paula A, Parra Cuentas E, Behrens C, Wistuba I, Zhang J, Blumenschein G, Gay C, Byers L, Gibbons D, Tsao A, Lee J, Bivona T, Camidge D, Gray J, Leighl N, Levy B, Brahmer J, Garassino M, Gandara D, Garon E, Rizvi N, Scagliotti G, Wolf J, Planchard D, Besse B, Herbst R, Wakelee H, Pennell N, Shaw A, Jänne P, Carbone D, Hellmann M, Rudin C, Albacker L, Mann H, Zhu Z, Lai Z, Stewart R, Peters S, Johnson M, Wong K, Huang A, Winslow M, Rosen M, Winters I, Papadimitrakopoulou V, Cascone T, Jewsbury P, Heymach J. Author Correction: CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature 2025, 639: e19-e19. PMID: 40016449, PMCID: PMC11903295, DOI: 10.1038/s41586-025-08767-9.Peer-Reviewed Original Research
2024
CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors
Skoulidis F, Araujo H, Do M, Qian Y, Sun X, Cobo A, Le J, Montesion M, Palmer R, Jahchan N, Juan J, Min C, Yu Y, Pan X, Arbour K, Vokes N, Schmidt S, Molkentine D, Owen D, Memmott R, Patil P, Marmarelis M, Awad M, Murray J, Hellyer J, Gainor J, Dimou A, Bestvina C, Shu C, Riess J, Blakely C, Pecot C, Mezquita L, Tabbó F, Scheffler M, Digumarthy S, Mooradian M, Sacher A, Lau S, Saltos A, Rotow J, Johnson R, Liu C, Stewart T, Goldberg S, Killam J, Walther Z, Schalper K, Davies K, Woodcock M, Anagnostou V, Marrone K, Forde P, Ricciuti B, Venkatraman D, Van Allen E, Cummings A, Goldman J, Shaish H, Kier M, Katz S, Aggarwal C, Ni Y, Azok J, Segal J, Ritterhouse L, Neal J, Lacroix L, Elamin Y, Negrao M, Le X, Lam V, Lewis W, Kemp H, Carter B, Roth J, Swisher S, Lee R, Zhou T, Poteete A, Kong Y, Takehara T, Paula A, Parra Cuentas E, Behrens C, Wistuba I, Zhang J, Blumenschein G, Gay C, Byers L, Gibbons D, Tsao A, Lee J, Bivona T, Camidge D, Gray J, Leighl N, Levy B, Brahmer J, Garassino M, Gandara D, Garon E, Rizvi N, Scagliotti G, Wolf J, Planchard D, Besse B, Herbst R, Wakelee H, Pennell N, Shaw A, Jänne P, Carbone D, Hellmann M, Rudin C, Albacker L, Mann H, Zhu Z, Lai Z, Stewart R, Peters S, Johnson M, Wong K, Huang A, Winslow M, Rosen M, Winters I, Papadimitrakopoulou V, Cascone T, Jewsbury P, Heymach J. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature 2024, 635: 462-471. PMID: 39385035, PMCID: PMC11560846, DOI: 10.1038/s41586-024-07943-7.Peer-Reviewed Original ResearchNon-small-cell lung cancerImmune checkpoint blockadeTumor suppressor genePD-L1Advanced non-small-cell lung cancerCD8+ cytotoxic T cellsSuppressor geneCD4+ effector cellsDual immune checkpoint blockadeMouse modelPD-L1 inhibitor durvalumabSuppressive myeloid cellsPD-L1 inhibitorsImmune-related toxicitiesPD-(L)1 inhibitorsAnti-tumor efficacyCytotoxic T cellsMyeloid cell compartmentAdverse tumor microenvironmentAssociated with higher ratesAnti-tumor activityLoss of Keap1CTLA4 inhibitorsSTK11 alterationsCheckpoint blockadeS4657 Heterogeneous Tumor Profiles in Hepatocellular Carcinoma: An Example of Late Recurrences With Genetically Distinct Tumors
Cao Y, Laurans M, Walther Z, Zhang X, Rose M, Taddei T. S4657 Heterogeneous Tumor Profiles in Hepatocellular Carcinoma: An Example of Late Recurrences With Genetically Distinct Tumors. The American Journal Of Gastroenterology 2024, 119: s2949-s2949. DOI: 10.14309/01.ajg.0001047996.50296.20.Peer-Reviewed Original ResearchASCL1 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, 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 cellsA destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition
Lenchner D, Petrova Z, Hunihan L, Ashtekar K, Walther Z, Wilson F. A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition. Npj Precision Oncology 2024, 8: 3. PMID: 38182677, PMCID: PMC10770066, DOI: 10.1038/s41698-023-00490-w.Peer-Reviewed Original Research
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 genesPlatinum 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 defectsCholangiocarcinomaTumors
Clinical Trials
Current Trials
Determining Mechanisms of Sensitivity and Resistance to Anti-Cancer Therapy for Advanced Lung Cancer
HIC ID1603017333RoleSub InvestigatorPrimary Completion Date06/20/2026Recruiting Participants
Clinical Care
Overview
Zenta Walther, MD, PhD, is the clinical director of the Yale New Haven Hospital Tumor Profiling Laboratory, and a pathologist who specializes in using molecular diagnostic techniques, especially next-generation sequencing, to analyze solid tumor tissues from patients. In particular, Dr. Walther looks for mutations within tumors that could be targeted with specific cancer drugs.
“I try to make personalized medicine possible for cancer patients,” Dr. Walther says. “And targeted therapies can often have fewer toxic side effects than conventional chemotherapy. I’m always eager to help patients find and enroll in available clinical trials.”
As an associate professor of pathology at Yale School of Medicine, Dr. Walther participates in translational research in addition to her clinical work. “By studying the genetic alterations in tumors before and after targeted therapy, we hope to gain new understanding that will lead to better treatment regimens and, ultimately, better outcomes for cancer patients.”
Clinical Specialties
Anatomic Pathology; Molecular & Genomic Pathology
Fact Sheets
Molecular Diagnostics
Learn More on Yale Medicine
Board Certifications
Anatomic Pathology
- Certification Organization
- AB of Pathology
- Original Certification Date
- 2001
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Locations
Department of Pathology
Academic Office
Clinic Building
789 Howard Avenue, Ste CB 565A
New Haven, CT 06519
Appointments
203.737.1347Fax
203.785.2641Patient Care Locations
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