Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment‐resistant melanoma, colorectal, and lung cancer
Theodosakis N, Langdon CG, Micevic G, Krykbaeva I, Means RE, Stern DF, Bosenberg MW. Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment‐resistant melanoma, colorectal, and lung cancer. Pigment Cell & Melanoma Research 2018, 32: 292-302. PMID: 30281931, PMCID: PMC6590911, DOI: 10.1111/pcmr.12742.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationColorectal NeoplasmsDrug Resistance, NeoplasmDrug SynergismHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLung NeoplasmsMaleMelanomaMevalonic AcidMice, NudeMitogen-Activated Protein KinasesPrenylationProtein Kinase InhibitorsProtein Processing, Post-TranslationalSignal TransductionConceptsUseful adjunctive therapyHMG-CoA reductase inhibitorsAnti-tumor effectsAdjunctive therapyInhibition of isoprenylationLung cancerMEK inhibitionReductase inhibitorsMAPK blockadeDriver mutationsAdditional studiesStatinsTherapyMelanomaTumorsVemurafenibMAPK pathwayDownstream metabolitesInhibitionMAPKAdjunctiveColorectalSelumetinibBlockadeCancerKeeping Tumors Out of the MAPK Fitness Zone
Stern DF. Keeping Tumors Out of the MAPK Fitness Zone. Cancer Discovery 2018, 8: 20-23. PMID: 29311225, DOI: 10.1158/2159-8290.cd-17-1243.Peer-Reviewed Original ResearchConceptsMAPK-targeted therapiesGreater fitnessMAPK signalingTumor cell subclonesMAPK pathwayCell deathERK inhibitorDNA damageTumor cell deathFitness barriersCell subclonesNew therapeutic approachesInhibitor withdrawalResistant clonesTherapeutic approachesTriple combinationMEKSignalingClonesSubclonesFitnessPathwayPatients