2020
Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin A
2017
Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer
Wali VB, Langdon CG, Held MA, Platt JT, Patwardhan GA, Safonov A, Aktas B, Pusztai L, Stern DF, Hatzis C. Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer. Cancer Research 2017, 77: 566-578. PMID: 27872098, PMCID: PMC5582957, DOI: 10.1158/0008-5472.can-16-1901.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBlotting, WesternCell Line, TumorCell ProliferationDrug Screening Assays, AntitumorDrug SynergismFemaleFlow CytometryHumansImmunoprecipitationPrincipal Component AnalysisTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTNBC cell linesPairwise drug combinationsClinical translationAggressive diseaseCombination therapyBreast cancerPreclinical proofDrug combinationsCombination treatmentInvestigational drugsSingle agentSensitivity patternCell sensitivityCell linesTherapyApoptotic activityAnticancer activityDownregulated genesMitogenic signalingCrizotinibBlockadeClinicAgentsCancer
2015
SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells
Langdon CG, Wiedemann N, Held MA, Mamillapalli R, Iyidogan P, Theodosakis N, Platt JT, Levy F, Vuagniaux G, Wang S, Bosenberg MW, Stern DF. SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells. Oncotarget 2015, 6: 37410-37425. PMID: 26485762, PMCID: PMC4741938, DOI: 10.18632/oncotarget.6138.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisApoptosis Regulatory ProteinsAzepinesAzocinesBenzhydryl CompoundsCamptothecinCell Line, TumorCell ProliferationDocetaxelDose-Response Relationship, DrugDrug SynergismFemaleHumansIrinotecanLung NeoplasmsMice, Inbred BALB CMice, NudeNF-kappa BPaclitaxelSignal TransductionTaxoidsTime FactorsTopoisomerase InhibitorsTriazolesTumor BurdenXenograft Model Antitumor AssaysConceptsLung adenocarcinoma cellsDebio 1143Adenocarcinoma cellsOngoing clinical trialsNon-canonical NF-κB signalingTopoisomerase inhibitorsLung adenocarcinoma xenograftsNF-κB signalingBromodomain inhibitor JQ1Clinical trialsConventional chemotherapyTumor volumeVivo treatmentAdenocarcinoma xenograftsAnti-apoptotic proteinsSingle agentCaspase-8 expressionVivo growthInhibitor JQ1Tumor cellsPro-apoptotic protein SmacJQ1Cell linesInhibitorsTaxanes
2008
Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B
DiGiovanna MP, Stern DF, Edgerton S, Broadwater G, Dressler LG, Budman DR, Henderson IC, Norton L, Liu ET, Muss HB, Berry DA, Hayes DF, Thor AD. Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B. Journal Of Clinical Oncology 2008, 26: 2364-2372. PMID: 18390970, PMCID: PMC6589994, DOI: 10.1200/jco.2007.13.6580.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDisease-Free SurvivalDose-Response Relationship, DrugDoxorubicinEnzyme ActivationFemaleFluorouracilGene DosageHumansImmunohistochemistryIn Situ Hybridization, FluorescenceLymphatic MetastasisNeoplasm StagingPhosphorylationReceptor, ErbB-2ConceptsLeukemia Group BAdjuvant cyclophosphamideErbB-2Breast cancerGroup BAnthracycline-based adjuvant chemotherapyNode-positive breast cancerAdverse prognostic factorSpecific chemotherapeutic agentsErbB-2 overexpressionActivation stateTumor tissue sectionsAdjuvant chemotherapyCAF doseCALGB 8541Fluorouracil chemotherapyPrognostic factorsAssessable casesFavorable outcomePatientsChemotherapeutic agentsStage IICancerDoseTissue sections