2024
Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer
Prasath V, Boutrid H, Wesolowski R, Abdel-Rasoul M, Timmers C, Lustberg M, Layman R, Macrae E, Mrozek E, Shapiro C, Glover K, Vater M, Budd G, Harris L, Isaacs C, Dees C, Perou C, Johnson G, Poklepovic A, Chen H, Villalona-Calero M, Carson W, Stover D, Ramaswamy B. Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer. Breast Cancer Research And Treatment 2024, 210: 179-189. PMID: 39644403, DOI: 10.1007/s10549-024-07551-z.Peer-Reviewed Original ResearchMetastatic triple negative breast cancerProgression-free survivalCirculating tumor DNATriple negative breast cancerTrametinib monotherapyNegative breast cancerStable diseasePartial responseBreast cancerCirculating tumor DNA clearanceMedian progression-free survivalClinical benefit rateMEK inhibitor trametinibPhase II studyBiomarkers of responseTreated with chemotherapyPotential early biomarkersInhibitor trametinibOpen-labelOverall survivalConclusionIn patientsDevelopment of resistanceObjective responseTumor DNABenefit rateA phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer
Planchard D, Wolf J, Solomon B, Sebastian M, Wermke M, Heist R, Sun J, Min Kim T, Reguart N, Sanmamed M, Felip E, Garrido P, Santoro A, Bootle D, Couillebault X, Gaur A, Mueller C, Poggio T, Yang J, Moschetta M, Dooms C. A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer. Lung Cancer 2024, 197: 107964. PMID: 39383771, DOI: 10.1016/j.lungcan.2024.107964.Peer-Reviewed Original ResearchNon-small cell lung cancerCell lung cancerBRAF-mutated non-small cell lung cancerLung cancerDose-escalation/dose-expansion studyTreatment-related adverse eventsAntitumor activityDose-limiting toxicityNRAS-mutant melanomaMEK1/2 inhibitor trametinibPartial responseInhibitor trametinibFrequent gradeSafety profileAdverse eventsPharmacodynamic effectsTrametinibGenetic alterationsMedian reductionPan-RAFIncreased lipasePatientsSecondary objectivesMRNA levelsEvaluate toleranceCombined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1
Hu R, Hou H, Li Y, Zhang M, Li X, Chen Y, Guo Y, Sun H, Zhao S, Liao M, Cao D, Yan Q, Chen X, Yin M. Combined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1. Theranostics 2024, 14: 593-607. PMID: 38169595, PMCID: PMC10758063, DOI: 10.7150/thno.85437.Peer-Reviewed Original ResearchConceptsMEK inhibitor resistanceMEK inhibitor trametinibTrametinib treatmentInhibitor resistanceInhibitor trametinibMelanoma patientsYAP1 expressionMEK inhibitionBRAF-mutant melanoma patientsResistance to MEK inhibitionYAP1 inhibitionResistance to trametinibMelanoma growth <i>inInhibition of BRD4Trametinib resistanceAntitumor effectMelanoma growthTrametinibNHWD-870YAP1 inhibitorDrug resistanceMelanomaMelanoma samplesMelanoma cellsBRD4 depletion
2014
Comprehensive Genomic Profiling of Pancreatic Acinar Cell Carcinomas Identifies Recurrent RAF Fusions and Frequent Inactivation of DNA Repair Genes
Chmielecki J, Hutchinson K, Frampton G, Chalmers Z, Johnson A, Shi C, Elvin J, Ali S, Ross J, Basturk O, Balasubramanian S, Lipson D, Yelensky R, Pao W, Miller V, Klimstra D, Stephens P. Comprehensive Genomic Profiling of Pancreatic Acinar Cell Carcinomas Identifies Recurrent RAF Fusions and Frequent Inactivation of DNA Repair Genes. Cancer Discovery 2014, 4: 1398-1405. PMID: 25266736, DOI: 10.1158/2159-8290.cd-14-0617.Peer-Reviewed Original ResearchConceptsPancreatic acinar cell carcinomaInactivation of DNA repair genesComprehensive genomic profilingDNA repair genesGenomic alterationsSensitive to platinum-based therapyRepair genesMEK inhibitor trametinibPlatinum-based therapyAcinar cell carcinomaPancreatic cancer diagnosisSensitive to treatmentInhibitor trametinibCell carcinomaMEK inhibitionPancreatic cancerPARP inhibitorsGenomic profilingApproximately 1%Personalized therapyRecurrent rearrangementsFrequent inactivationTumorTherapeutic targetRAF genes
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