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, 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 cellsHER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial
Li Z, Filho O, Viale G, dell'Orto P, Russo L, Goyette M, Kamat A, Yardley D, Abramson V, Arteaga C, Spring L, Chiotti K, Halsey C, Waks A, King T, Lester S, Bellon J, Winer E, Spellman P, Krop I, Polyak K. HER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial. Journal Of Clinical Investigation 2024, 134: e176454. PMID: 38300710, PMCID: PMC10977978, DOI: 10.1172/jci176454.Peer-Reviewed Original ResearchPathological complete responseHER2-positive breast cancerHER2 heterogeneityBreast cancerEarly-stage HER2-positive breast cancerHER2-targeted therapyPre-treatment tumorsErbB signalingHER2-targeted antibodiesBasal-like featuresHER2 protein levelsStratification of patientsNational Cancer InstituteNeoadjuvant trialsComplete responseResidual tumorT-DM1Copy number heterogeneityTrastuzumab emtansineERBB2 mRNAImmune infiltrationDownstream pathway componentsClinical challengeClinical trialsTumor
2021
Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer
Keenan TE, Guerriero JL, Barroso-Sousa R, Li T, O’Meara T, Giobbie-Hurder A, Tayob N, Hu J, Severgnini M, Agudo J, Vaz-Luis I, Anderson L, Attaya V, Park J, Conway J, He MX, Reardon B, Shannon E, Wulf G, Spring LM, Jeselsohn R, Krop I, Lin NU, Partridge A, Winer EP, Mittendorf EA, Liu D, Van Allen EM, Tolaney SM. Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer. Nature Communications 2021, 12: 5563. PMID: 34548479, PMCID: PMC8455578, DOI: 10.1038/s41467-021-25769-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntigen PresentationAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBreast NeoplasmsCytokinesDrug Resistance, NeoplasmEstrogensFemaleFuransGene Expression ProfilingGenetic HeterogeneityGenome, HumanGenomicsHumansImmune Checkpoint InhibitorsKetonesLymphocytes, Tumor-InfiltratingMaleMiddle AgedMutationNeoplasm MetastasisReceptors, EstrogenReceptors, ProgesteroneSignal TransductionSurvival RateTreatment OutcomeConceptsImmune checkpoint inhibitorsBreast cancerHormone receptor-positive metastatic breast cancerHormone receptor-positive breast cancerFinal overall survival resultsRandomized phase 2 trialReceptor-positive breast cancerMinimal therapeutic effectPhase 2 trialMetastatic breast cancerOverall survival resultsPre-treatment tumorsCheckpoint inhibitorsCytokine changesICI responseCombination therapyImmune infiltrationImmunoregulatory cytokinesSurvival resultsAntigen presentationTherapeutic effectTherapeutic validationCancerMolecular correlatesTumor heterogeneity
2019
Heterogeneous Genetic Alterations and Novel Pathogenic Pathways in Relapsed DLBCL Revealed By Whole Exome Sequencing
Ma J, Nie K, Inghirami G, Eng K, Elemento O, Au-Yeung R, Shen Y, Srivastava G, Gong J, Xu M, Tan L, Tam W. Heterogeneous Genetic Alterations and Novel Pathogenic Pathways in Relapsed DLBCL Revealed By Whole Exome Sequencing. Blood 2019, 134: 2770. DOI: 10.1182/blood-2019-125448.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaRelapsed diffuse large B-cell lymphomaWhole-exome sequencingPre-treatment tumorsVariant allele frequencyPre-treatment samplesAxonal guidance signalingRelapse samplesR-CHOPNormal controlsDLBCL cohortProgression-free survival ratesReceptor signalingExome sequencingLarge B-cell lymphomaFree survival rateFront-line treatmentILK signalingThird of patientsAryl hydrocarbon receptor signalingNovel therapeutic approachesB-cell lymphomaGuidance signalingNovel pathogenic pathwaysInstitutional review boardGenomic-based predictive biomarkers to anti-HER2 therapies: A combined analysis of CALGB 40601 (Alliance) and PAMELA clinical trials.
Fernandez-Martinez A, Tanioka M, Fan C, Parker J, Hoadley K, Krop I, Cortes J, Llombart Cussac A, Nuciforo P, Galván P, Pascual T, Partridge A, Prat A, Carey L, Perou C. Genomic-based predictive biomarkers to anti-HER2 therapies: A combined analysis of CALGB 40601 (Alliance) and PAMELA clinical trials. Journal Of Clinical Oncology 2019, 37: 571-571. DOI: 10.1200/jco.2019.37.15_suppl.571.Peer-Reviewed Original ResearchHER2-E subtypeCALGB 40601Clinical trialsPredictive biomarkersIntrinsic subtypesEvent-free survival analysisHER2-positive breast cancerAnti-HER2 combinationDual HER2 blockadeAnti-HER2 therapyAnti-HER2 treatmentIndependent predictive biomarkerFree survival analysisPre-treatment tumorsERBB2 mRNA levelsHER2 blockadeLuminal signatureNeoadjuvant settingPCR rateIndependent predictorsLuminal ALuminal BSubtype distributionBreast cancerERBB2 mRNA
2015
Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
Baine MK, Turcu G, Zito CR, Adeniran AJ, Camp RL, Chen L, Kluger HM, Jilaveanu LB. Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens. Oncotarget 2015, 6: 24990-25002. PMID: 26317902, PMCID: PMC4694809, DOI: 10.18632/oncotarget.4572.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedB7-H1 AntigenCarcinoma, Renal CellCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleFluorescent Antibody TechniqueForkhead Transcription FactorsHumansKidney NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm MetastasisTissue Array AnalysisYoung AdultConceptsRenal cell carcinomaT cell ratioMetastatic specimensPD-L1Cell carcinomaPD-1/PD-L1 blockadePD-1/PD-L1 statusPD-1/PD-L1 pathwayMetastatic renal cell carcinomaHigh PD-L1PD-L1 blockadeUnfavorable tumor characteristicsPD-L1 expressionPD-L1 statusPD-L1 pathwayT-cell contentPre-treatment tumorsLow CD8TIL subsetsCharacterization of tumorsTIL densitySuch patientsTumor characteristicsImmune activationPatient survival
2013
Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel
Jilaveanu LB, Zhao F, Zito CR, Kirkwood JM, Nathanson KL, D'Andrea K, Wilson M, Rimm DL, Flaherty KT, Lee SJ, Kluger HM. Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel. PLOS ONE 2013, 8: e69748. PMID: 23936348, PMCID: PMC3735539, DOI: 10.1371/journal.pone.0069748.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalVEGF-R1FGF-R1Paclitaxel-based therapyVEGF-R1 expressionPre-treatment tumorsPredictive biomarker signaturesMultitarget kinase inhibitorPDGF-RβSitu protein expressionTherapeutic ratioTaxane sensitivityMitogen-activated protein kinase pathwayPatientsVEGF-R3CarboplatinSorafenibVEGF-R2C-kitKinase inhibitorsTherapyProtein expressionPhase IIISorafenib targets
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