2022
Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu
Yadav G, Roque DM, Bellone S, Manavella DD, Hartwich TMP, Zipponi M, Harold J, Tymon-Rosario J, Mutlu L, Altwerger G, Menderes G, Ratner E, Buza N, Hui P, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu. Gynecologic Oncology 2022, 166: 351-357. PMID: 35641325, DOI: 10.1016/j.ygyno.2022.05.021.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaHER2/neu expressionHER2/neuCombination of olaparibUSC xenograftsUSC cell linesNeu expressionSerous carcinomaLow HER2/neu expressionHER2/neu 3Cell linesHER2/neu gene amplificationNovel therapeutic optionsPolymerase inhibitor olaparibNeu gene amplificationDurable growth inhibitionNeratinib treatmentUSC cellsUSC patientsEndometrial cancerAggressive variantTherapeutic optionsPoor prognosisHER2/Single agent
2015
Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo
Lopez S, Cocco E, Black J, Bellone S, Bonazzoli E, Predolini F, Ferrari F, Schwab CL, English DP, Ratner E, Silasi DA, Azodi M, Schwartz PE, Terranova C, Angioli R, Santin AD. Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo. Molecular Cancer Therapeutics 2015, 14: 2519-2526. PMID: 26333383, PMCID: PMC4636465, DOI: 10.1158/1535-7163.mct-15-0383.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell CycleCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCystadenocarcinoma, SerousDose-Response Relationship, DrugDrug SynergismFemaleGene AmplificationHumansImidazolesImmunoblottingMice, SCIDMutationOxazepinesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationQuinolinesReceptor, ErbB-2Uterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neu gene amplificationNeu gene amplificationUSC xenograftsUterine serous carcinomaGene amplificationUterine serous carcinoma cell linesSingle-agent therapyNovel therapeutic optionsWild-type PIK3CADose-dependent increaseIdeal therapeutic targetUSC cell linesCell linesDose-dependent declineFlow cytometry assayG0-G1 phaseCell cycle distributionOncogenic PIK3CA mutationsPercentage of cellsUSC patientsEndometrial cancerAggressive variantSerous carcinomaTherapeutic optionsCarcinoma cell linesDacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro
Zhu L, Lopez S, Bellone S, Black J, Cocco E, Zigras T, Predolini F, Bonazzoli E, Bussi B, Stuhmer Z, Schwab CL, English DP, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro. Tumor Biology 2015, 36: 5505-5513. PMID: 25669172, PMCID: PMC5573583, DOI: 10.1007/s13277-015-3218-4.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaReceptor tyrosine kinase inhibitorsHER2/neu gene amplificationTyrosine kinase inhibitorsUSC cell linesNeu gene amplificationEndometrial cancerIrreversible pan-ErbB receptor tyrosine kinase inhibitorEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsEpidermal growth factor receptor 2Cell linesKinase inhibitorsEffect of dacomitinibStandard salvage chemotherapyGrowth factor receptor 2Serous endometrial cancerFlow cytometry-based assayHER2/neuFactor receptor 2Dose-dependent declineGene amplificationCell cycle distributionCytometry-based assayGrowth inhibition
2014
Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo
Schwab CL, Bellone S, English DP, Roque DM, Lopez S, Cocco E, Nicoletti R, Bortolomai I, Bonazzoli E, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo. British Journal Of Cancer 2014, 111: 1750-1756. PMID: 25268372, PMCID: PMC4453741, DOI: 10.1038/bjc.2014.519.Peer-Reviewed Original ResearchMeSH KeywordsAdultAfatinibAgedAged, 80 and overAnimalsApoptosisCell CycleCell ProliferationCystadenocarcinoma, SerousEndometrial NeoplasmsFemaleHumansImmunoenzyme TechniquesIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMice, SCIDMiddle AgedPhosphorylationQuinazolinesReceptor, ErbB-2Signal TransductionTumor Cells, CulturedUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaUSC cell linesHER2/neu gene amplificationNeu gene amplificationAfatinib exposureOverall survivalCell linesHER2/neu amplificationEfficacy of afatinibPrimary USC cell linesGrowth of HER2Treatment of HER2Serous endometrial cancerErbB tyrosine kinase inhibitorsHER2/neuTyrosine kinase inhibitorsGene amplificationFlow cytometry assayCell cycle distributionUSC xenograftsEndometrial cancerSerous carcinomaUterine cancerAggressive formTumor xenograftsTaselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo
Lopez S, Schwab CL, Cocco E, Bellone S, Bonazzoli E, English DP, Schwartz PE, Rutherford T, Angioli R, Santin AD. Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecologic Oncology 2014, 135: 312-317. PMID: 25172762, PMCID: PMC4270135, DOI: 10.1016/j.ygyno.2014.08.024.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntineoplastic AgentsCarcinomaCell Cycle CheckpointsCell Line, TumorCell ProliferationClass I Phosphatidylinositol 3-KinasesDrug Screening Assays, AntitumorFemaleGene AmplificationHumansImidazolesIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOxazepinesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsReceptor, ErbB-2Uterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neu gene amplificationUterine serous carcinomaUSC cell linesNeu gene amplificationCell linesHER2/neuPIK3CA mutationsGene amplificationPhosphorylation of S6Serous carcinomaPIK3CA wild typeG0/G1 phaseSelective inhibitorOncogenic PIK3CA mutationsS6 proteinCell cycle distributionPrimary uterine serous carcinomaWild typeDownstream signalingPrimary USC cell linesCell cycleNovel therapeutic optionsDose-dependent increaseDifferential growth inhibitionG1 phase
2013
HER2/neu gene amplification determines the sensitivity of uterine serous carcinoma cell lines to AZD8055, a novel dual mTORC1/2 inhibitor
English DP, Roque DM, Carrara L, Lopez S, Bellone S, Cocco E, Bortolomai I, Schwartz PE, Rutherford T, Santin AD. HER2/neu gene amplification determines the sensitivity of uterine serous carcinoma cell lines to AZD8055, a novel dual mTORC1/2 inhibitor. Gynecologic Oncology 2013, 131: 753-758. PMID: 24012800, DOI: 10.1016/j.ygyno.2013.08.033.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCarcinoma, PapillaryCell Line, TumorCystadenocarcinoma, SerousFemaleGene AmplificationHumansMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MorpholinesMultiprotein ComplexesProtein Kinase InhibitorsReceptor, ErbB-2TOR Serine-Threonine KinasesUterine NeoplasmsConceptsUSC cell linesC-erbB2 gene amplificationUterine serous carcinoma cell linesDual mTORC1/2 inhibitorCarcinoma cell linesC-erbB2Cell linesGene amplificationMTORC1/2 inhibitorsPrimary USC cell linesHER2/neu gene amplificationG0/G1 cell cycle phaseDose-dependent increaseHigh HER-2HER2/neuNeu gene amplificationDose-dependent declinePercentage of cellsUSC patientsHER-2Cell cycle profileDifferential growth inhibitionG1 cell cycle phasePS6 levelsTherapeutic agentsOncogenic PIK3CA gene mutations and HER2/neu gene amplifications determine the sensitivity of uterine serous carcinoma cell lines to GDC-0980, a selective inhibitor of Class I PI3 kinase and mTOR kinase (TORC1/2)
English DP, Bellone S, Cocco E, Bortolomai I, Pecorelli S, Lopez S, Silasi DA, Schwartz PE, Rutherford T, Santin AD. Oncogenic PIK3CA gene mutations and HER2/neu gene amplifications determine the sensitivity of uterine serous carcinoma cell lines to GDC-0980, a selective inhibitor of Class I PI3 kinase and mTOR kinase (TORC1/2). American Journal Of Obstetrics And Gynecology 2013, 209: 465.e1-465.e9. PMID: 23891627, DOI: 10.1016/j.ajog.2013.07.020.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicCarcinoma, PapillaryCell Line, TumorClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleGene AmplificationGenes, erbB-2HumansIn Situ Hybridization, FluorescenceMiddle AgedMutationPhosphatidylinositol 3-KinasesPyrimidinesTOR Serine-Threonine KinasesConceptsClass I PI3-kinasePI3-kinaseC-erbB2 gene amplificationOncogenic PIK3CA mutationsMTOR kinaseCell linesGene amplificationUterine serous carcinoma cell linesDownstream cellular responsesCarcinoma cell linesUSC cell linesGene mutationsCellular responsesKinaseDifferential growth inhibitionDNA sequencingDirect DNA sequencingMutationsSitu hybridizationUse of GDCGrowth inhibitionExon 9HER2/neu gene amplificationFishPrimary USC cell lines