2017
p90RSK Blockade Inhibits Dual BRAF and MEK Inhibitor-Resistant Melanoma by Targeting Protein Synthesis
Theodosakis N, Micevic G, Langdon CG, Ventura A, Means R, Stern DF, Bosenberg MW. p90RSK Blockade Inhibits Dual BRAF and MEK Inhibitor-Resistant Melanoma by Targeting Protein Synthesis. Journal Of Investigative Dermatology 2017, 137: 2187-2196. PMID: 28599981, PMCID: PMC6342201, DOI: 10.1016/j.jid.2016.12.033.Peer-Reviewed Original ResearchConceptsProtein synthesisRibosomal S6 kinase (RSK) familyPatient-derived melanoma cell linesDifferential protein expressionReverse phase protein arrayPhase protein arrayTranslation complexesKinase familyBI-D1870RSK inhibitorsMelanoma cell linesProtein arraysCell proliferationInhibitor treatmentProtein expressionCell linesNew targetsHuman melanoma patientsBRAF inhibitor vemurafenib
2015
BRAF Inhibition Decreases Cellular Glucose Uptake in Melanoma in Association with Reduction in Cell Volume
Theodosakis N, Held MA, Marzuka-Alcala A, Meeth KM, Micevic G, Long GV, Scolyer RA, Stern DF, Bosenberg MW. BRAF Inhibition Decreases Cellular Glucose Uptake in Melanoma in Association with Reduction in Cell Volume. Molecular Cancer Therapeutics 2015, 14: 1680-1692. PMID: 25948295, PMCID: PMC4497841, DOI: 10.1158/1535-7163.mct-15-0080.Peer-Reviewed Original ResearchConceptsGlucose uptakeWeeks of treatmentBRAF kinase inhibitorsHigh response rateTumor cell deathMetastatic diseaseTransmembrane glucose transportMetastatic melanomaPatient cohortCellular glucose uptakeRadiographic changesVemurafenib treatmentBRAF inhibitorsBRAF inhibitionResponse rateEmission tomographyPhysiologic parametersNew protein translationKinase inhibitorsEarly responseImportant physiologic parametersCell volumeMelanomaVolume reductionCell volume regulationmTORC1 Activation Blocks Braf V600E -Induced Growth Arrest but Is Insufficient for Melanoma Formation
Damsky W, Micevic G, Meeth K, Muthusamy V, Curley DP, Santhanakrishnan M, Erdelyi I, Platt JT, Huang L, Theodosakis N, Zaidi MR, Tighe S, Davies MA, Dankort D, McMahon M, Merlino G, Bardeesy N, Bosenberg M. mTORC1 Activation Blocks Braf V600E -Induced Growth Arrest but Is Insufficient for Melanoma Formation. Cancer Cell 2015, 27: 41-56. PMID: 25584893, PMCID: PMC4295062, DOI: 10.1016/j.ccell.2014.11.014.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsCell Line, TumorCell ProliferationCyclin-Dependent Kinase Inhibitor p16HumansMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MelanocytesMelanoma, ExperimentalMiceMicroRNAsMolecular Sequence DataMultiprotein ComplexesMutationNevusProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafSignal TransductionSkin NeoplasmsTOR Serine-Threonine KinasesConceptsMelanoma formationGrowth arrestStable growth arrestMTORC2/AktSTK11 lossCDKN2A lossAkt activationIGF1R signalingMice resultsActivationArrestMTORC2Nevus developmentMTORC1/2SignalingAktMelanocytic nevus developmentMelanomagenesisMTORProgressionCDKN2AMelanocytesInactivationUpregulationComplete progression