2015
PDK1 and SGK3 Contribute to the Growth of BRAF-Mutant Melanomas and Are Potential Therapeutic Targets
Scortegagna M, Lau E, Zhang T, Feng Y, Sereduk C, Yin H, De SK, Meeth K, Platt JT, Langdon CG, Halaban R, Pellecchia M, Davies MA, Brown K, Stern DF, Bosenberg M, Ronai ZA. PDK1 and SGK3 Contribute to the Growth of BRAF-Mutant Melanomas and Are Potential Therapeutic Targets. Cancer Research 2015, 75: 1399-1412. PMID: 25712345, PMCID: PMC4383687, DOI: 10.1158/0008-5472.can-14-2785.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzoatesBridged Bicyclo Compounds, HeterocyclicCell Line, TumorDrug Screening Assays, AntitumorG1 Phase Cell Cycle CheckpointsHumansImmediate-Early ProteinsIndazolesLymphatic MetastasisMelanomaMice, KnockoutMolecular Targeted TherapyProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafPyrimidinesPyruvate Dehydrogenase Acetyl-Transferring KinaseSkinSkin NeoplasmsConceptsPDK1 inhibitionAGC kinase familySynthetic lethal screenCell cycle arrestPhase cell cycle arrestPigmentation genesPDK1 activityG1 phase cell cycle arrestSuppress melanoma growthKinase familyTherapeutic targetMelanoma growthPDK1PTEN genotypePI3KMelanoma developmentPotential therapeutic targetK inhibitionPharmacologic inhibitionDevelopment of melanomaPan-PI3K inhibitionBRAF-mutant melanomaSGK3GenesMelanoma cells
2012
Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors
Shi H, Moriceau G, Kong X, Koya RC, Nazarian R, Pupo GM, Bacchiocchi A, Dahlman KB, Chmielowski B, Sosman JA, Halaban R, Kefford RF, Long GV, Ribas A, Lo RS. Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors. Cancer Discovery 2012, 2: 414-424. PMID: 22588879, PMCID: PMC3594852, DOI: 10.1158/2159-8290.cd-12-0022.Peer-Reviewed Original ResearchConceptsBRAF inhibitorsActivating mutationsObjective tumor responseMEK1/2 inhibitorMEK1 mutationsP-ERK1/2 levelsBRAF-mutant melanomaMelanoma cell linesAdvanced melanomaAntitumor responseExon 3 mutationsTumor responseDisease progressionMelanomaBRAFi resistanceDrug sensitivitySignificant alterationsPatientsCell linesInhibitorsBaselineMutationsExon 3Widespread use