2020
Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma
Bonazzoli E, Bellone S, Zammataro L, Gnutti B, Guglielmi A, Pelligra S, Nagarkatti N, Manara P, Tymon-Rosario J, Zeybek B, Altwerger G, Menderes G, Han C, Ratner E, Silasi DA, Huang GS, Andikyan V, Azodi M, Schwartz PE, Santin AD. Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma. Gynecologic Oncology 2020, 158: 769-775. PMID: 32600791, PMCID: PMC8253557, DOI: 10.1016/j.ygyno.2020.06.484.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsCell Line, TumorFemaleHumansImidazolesIn Situ Hybridization, FluorescenceIsoxazolesMiceMiddle AgedProteinsProto-Oncogene Proteins c-mycSignal TransductionTumor Suppressor ProteinsUbiquitin-Protein LigasesUterine Cervical NeoplasmsXenograft Model Antitumor AssaysYoung AdultConceptsC-myc expressionC-Myc pathwayTwice-daily oral dosesC-MycWestern blotChemotherapy-resistant diseaseUterine cervical carcinomaPotential therapeutic targetEffective therapeutic agentDose-response decreaseCC xenograftsCell line growthOral dosesCervical carcinomaPrimary tumorDeletion/mutationClinical studiesTherapeutic targetTherapeutic agentsNormal tissuesBET inhibitorsVivo activityQRT-PCRCell proliferationGene deletion/mutation
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 lines
2014
Taselisib, 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