2013
Preclinical and Clinical Studies of Gamma Secretase Inhibitors with Docetaxel on Human Breast Tumors
Schott AF, Landis MD, Dontu G, Griffith KA, Layman RM, Krop I, Paskett LA, Wong H, Dobrolecki LE, Lewis MT, Froehlich AM, Paranilam J, Hayes DF, Wicha MS, Chang JC. Preclinical and Clinical Studies of Gamma Secretase Inhibitors with Docetaxel on Human Breast Tumors. Clinical Cancer Research 2013, 19: 1512-1524. PMID: 23340294, PMCID: PMC3602220, DOI: 10.1158/1078-0432.ccr-11-3326.Peer-Reviewed Original ResearchConceptsBreast cancer stem cellsGamma-secretase inhibitorsAdvanced breast cancerClinical trialsBreast cancerSecretase inhibitorsMaximum-tolerated doseEfficacy of docetaxelSerial tumor biopsiesNotch pathwayTumors of patientsDoses of MKConcurrent clinical trialsHuman breast tumorsNotch pathway inhibitorsCancer stem cellsManageable toxicityTumorgraft modelsDocetaxel treatmentBCSC markersSerial biopsiesConventional therapyPreclinical dataClinical studiesExperimental therapies
2012
Phase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors
Krop I, Demuth T, Guthrie T, Wen PY, Mason WP, Chinnaiyan P, Butowski N, Groves MD, Kesari S, Freedman SJ, Blackman S, Watters J, Loboda A, Podtelezhnikov A, Lunceford J, Chen C, Giannotti M, Hing J, Beckman R, LoRusso P. Phase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2012, 30: 2307-2313. PMID: 22547604, DOI: 10.1200/jco.2011.39.1540.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsClinical benefitDose levelsSolid tumorsCommon drug-related toxicitiesGene signatureObjective complete responsePreliminary antitumor efficacyWeekly dose levelMaximum-tolerated doseDose-proportional mannerDrug-related toxicityHigh-grade gliomasHighest dose levelStable diseaseWeekly dosingAdult patientsComplete responseOral inhibitorNotch signalingCombination trialsNovel agentsPharmacodynamic studiesPatientsNotch pathway activation