2021
Sapanisertib, a dual mTORC1/2 inhibitor, for TSC1- or TSC2- mutated metastatic urothelial carcinoma (mUC).
Kim J, Milowsky M, Hahn N, Kwiatkowski D, Morgans A, Davis N, Appleman L, Gupta S, Lara P, Hoffman-Censits J, Quinn D, Shyr Y, LoRusso P, Sklar J, Petrylak D. Sapanisertib, a dual mTORC1/2 inhibitor, for TSC1- or TSC2- mutated metastatic urothelial carcinoma (mUC). Journal Of Clinical Oncology 2021, 39: 431-431. DOI: 10.1200/jco.2021.39.6_suppl.431.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaStable diseaseAdverse eventsObjective responseWithdrew consentTSC2 mutationsUrothelial carcinomaTSC1 mutationsTumor samplesCommon adverse eventsMedian overall survivalTreatment-related deathsPhase II studyCentral labOverall response rateDual mTORC1/2 inhibitorUnknown mutational statusCentral confirmationEligible patientsEvaluable patientsMUC patientsRestaging scanII studyPrimary endpointBaseline characteristics
2013
The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma stem-like cells
Kahn J, Hayman T, Jamal M, Rath B, Kramp T, Camphausen K, Tofilon P. The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma stem-like cells. Neuro-Oncology 2013, 16: 29-37. PMID: 24311635, PMCID: PMC3870843, DOI: 10.1093/neuonc/not139.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBenzamidesBrain NeoplasmsCell CycleCell ProliferationDNA Breaks, Double-StrandedDNA RepairFemaleFluorescent Antibody TechniqueGlioblastomaHistonesHumansMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MiceMice, NudeMorpholinesMultiprotein ComplexesNeoplastic Stem CellsProtein Kinase InhibitorsPyrimidinesRadiation-Sensitizing AgentsTOR Serine-Threonine KinasesTumor Cells, CulturedX-Ray TherapyXenograft Model Antitumor AssaysConceptsGBM stem-like cellsDual mTORC1/2 inhibitorStem-like cellsOrthotopic xenograftsMTORC1/2 inhibitorsPrimary treatment modalityΓH2AX fociRadiation-induced γH2AX fociGlioblastoma stem-like cellsTreatment modalitiesClonogenic survival analysisGBM therapyMTOR inhibitorsSurvival analysisGSC cell linesClonogenic assayMammalian targetVivo responseAZD2014GlioblastomaIndividual treatmentRadiosensitivityCell linesXenograftsImmunoblot analysisHER2/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 agents
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