2023
Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency
Stecklein S, Barlow W, Pusztai L, Timms K, Kennedy R, Logan G, Seitz R, Badve S, Gökmen-Polar Y, Porter P, Linden H, Tripathy D, Hortobagyi G, Godwin A, Thompson A, Hayes D, Sharma P. Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency. JCO Precision Oncology 2023, 7: e2300197. PMID: 37972336, PMCID: PMC10681491, DOI: 10.1200/po.23.00197.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerHomologous recombination deficiencyBreast cancerAdjuvant anthracycline-based chemotherapyTherapeutic vulnerabilitiesRecombination deficiencyDistinct therapeutic vulnerabilitiesAnthracycline-based chemotherapyImmune response signaturesDNA-damaging therapiesFavorable prognosisIntermediate prognosisWorse prognosisImmunologic microenvironmentImmune responseChemoresistant tumorsPrognostic classificationHeterogeneous diseasePrognosisHeterogeneous groupDistinct subgroupsTumorsCancerResponse signatureSimultaneous assessment
2021
Diverse immune response of DNA damage repair-deficient tumors
Qing T, Jun T, Lindblad KE, Lujambio A, Marczyk M, Pusztai L, Huang KL. Diverse immune response of DNA damage repair-deficient tumors. Cell Reports Medicine 2021, 2: 100276. PMID: 34095878, PMCID: PMC8149377, DOI: 10.1016/j.xcrm.2021.100276.Peer-Reviewed Original ResearchConceptsCancer typesDDR-deficient tumorsImmune checkpoint inhibitorsHigh neoantigen loadDifferent immune phenotypesDiverse immune responsesAdaptive immune markersRepair-deficient tumorsDDR deficiencyCheckpoint inhibitorsImmunotherapy outcomesDNA damage repair deficiencyImmune infiltratesImmune markersNeoantigen loadSurvival outcomesImmune phenotypeTumor neoantigensImmune responseAnimal modelsGenomic biomarkersGermline mutationsPathway mutationsTumorsRepair deficiency
2019
Validation of the DNA Damage Immune Response Signature in Patients With Triple-Negative Breast Cancer From the SWOG 9313c Trial.
Sharma P, Barlow WE, Godwin AK, Parkes EE, Knight LA, Walker SM, Kennedy RD, Harkin DP, Logan GE, Steele CJ, Lambe SM, Badve S, Gökmen-Polar Y, Pathak HB, Isakova K, Linden HM, Porter P, Pusztai L, Thompson AM, Tripathy D, Hortobagyi GN, Hayes DF. Validation of the DNA Damage Immune Response Signature in Patients With Triple-Negative Breast Cancer From the SWOG 9313c Trial. Journal Of Clinical Oncology 2019, 37: 3484-3492. PMID: 31657982, PMCID: PMC7194448, DOI: 10.1200/jco.19.00693.Peer-Reviewed Original ResearchConceptsStromal tumor-infiltrating lymphocytesTriple-negative breast cancerDisease-free survivalOverall survivalImmune response signaturesBreast cancerEarly-stage triple-negative breast cancerThree-year disease-free survivalParaffin-embedded tumor tissueThird of patientsTumor-infiltrating lymphocytesSubgroup of patientsCox regression modelResponse signatureAdjuvant ACAdjuvant doxorubicinSTIL densityT2N0 diseaseAC chemotherapyNodal statusPrognostic roleImproved prognosisPrognostic valueTumor sizePrognostic marker
2017
Structural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer
Chen C, Gu P, Wu J, Chen X, Niu S, Sun H, Wu L, Li N, Peng J, Shi S, Fan C, Huang M, Wong CC, Gong Q, Kumar-Sinha C, Zhang R, Pusztai L, Rai R, Chang S, Lei M. Structural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer. Nature Communications 2017, 8: 14929. PMID: 28393832, PMCID: PMC5394241, DOI: 10.1038/ncomms14929.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsConserved SequenceDNA DamageDNA Mutational AnalysisDNA RepairGenomic InstabilityHumansMiceModels, MolecularMolecular ChaperonesMutationNeoplasmsPhosphoproteinsProstaglandin-E SynthasesProtein BindingProtein Structure, SecondaryScattering, Small AngleShelterin ComplexStructure-Activity RelationshipTelomere-Binding ProteinsX-Ray DiffractionConceptsTelomerase-mediated telomere extensionHuman cancersDNA damage responseC-terminal mutationsOB foldsHuman POT1Chromosome endsGenome instabilityPOT1-TPP1Telomere extensionDamage responseStable heterodimerA-NHEJStructural insightsC-terminusInappropriate repairTPP1POT1Heart-shaped structureMissense mutationsTerminal portionMutationsDomainMutantsTelomeres
1998
Physiologic and Pathologic Drug Resistance in Ovarian Carcinoma: A Hypothesis Based on a Clonal Progression Model
Pusztai L, Siddik Z, Mills G, Bast R. Physiologic and Pathologic Drug Resistance in Ovarian Carcinoma: A Hypothesis Based on a Clonal Progression Model. Acta Oncologica 1998, 37: 629-640. PMID: 10050979, DOI: 10.1080/028418698429964.Peer-Reviewed Original ResearchConceptsEarly-stage ovarian cancerDrug-resistant cellsDrug resistanceDrug sensitivityOvarian cancerTumor progressionDisease-free survivalHigh-dose chemotherapyNumerous clinical studiesDifferent treatment strategiesCell populationsHigh response rateCorresponding normal tissuesInsufficient chemotherapyAdjuvant chemotherapyIntensive chemotherapyAdvanced diseaseClinical responseCombination chemotherapyConventional dosesMolecular biological observationsOvarian carcinomaPhysiological drug resistanceClinical failureClinical studies