2016
Phase I study of safety and tolerability of sunitinib in combination with sirolimus in patients with refractory solid malignancies and determination of VEGF (VEGF-A) and soluble VEGF-R2 (sVEGFR2) in plasma
Li J, Kluger H, Devine L, Lee JJ, Kelly WK, Rink L, Saif MW. Phase I study of safety and tolerability of sunitinib in combination with sirolimus in patients with refractory solid malignancies and determination of VEGF (VEGF-A) and soluble VEGF-R2 (sVEGFR2) in plasma. Cancer Chemotherapy And Pharmacology 2016, 77: 1193-1200. PMID: 27103123, DOI: 10.1007/s00280-016-3033-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansIndolesMaleMaximum Tolerated DoseMiddle AgedNeoplasmsPyrrolesSirolimusSunitinibTOR Serine-Threonine KinasesVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Young AdultConceptsRenal cell carcinomaComplete responseFourth cohortVEGF productionOral small-molecule inhibitorApparent pharmacokinetic interactionMedian age 57Prior systemic therapyRefractory solid malignanciesResidual renal massTolerability of sunitinibHand-foot syndromeHalf of patientsLymph node dissectionCombination of sunitinibPhase 1 studyDose of sunitinibOral mTOR inhibitorDose/scheduleUnknown compensatory mechanismsCycle 1Multiple receptor tyrosine kinasesAnti-tumor activityEpithelial growth factor receptor (EGFR) signalingTumor cell proliferation
2011
Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer
Elfiky AA, Aziz SA, Conrad PJ, Siddiqui S, Hackl W, Maira M, Robert CL, Kluger HM. Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer. Journal Of Translational Medicine 2011, 9: 133. PMID: 21834980, PMCID: PMC3173341, DOI: 10.1186/1479-5876-9-133.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisAutomationBiomarkers, TumorCarcinoma, Renal CellCell Line, TumorChromonesDrug SynergismHumansImidazolesInhibitory Concentration 50Kidney NeoplasmsMolecular Targeted TherapyMorpholinesMultivariate AnalysisPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsQuinolinesSirolimusTOR Serine-Threonine KinasesConceptsRenal cell carcinomaRCC cell linesNVP-BEZ235PI3KMTOR expressionMetastatic renal cell carcinomaPI3K subunitsHigh mTOR expressionAutomated Quantitative AnalysisRCC cell growthRenal cell cancerExpression of p85PI3K inhibitor LY294002Cell linesWarrants further investigationK inhibitor LY294002PI3K inhibitorsMulti-variable analysisCell cancerCell carcinomaClinical trialsSitu protein expressionNephrectomy casesTissue microarrayMTOR inhibitors