2018
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 metabolitesInhibitionMAPKAdjunctiveColorectalSelumetinibBlockadeCancer
2017
Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor
Langdon CG, Platt JT, Means RE, Iyidogan P, Mamillapalli R, Klein M, Held MA, Lee JW, Koo JS, Hatzis C, Hochster HS, Stern DF. Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor. Molecular Cancer Therapeutics 2017, 16: 1041-1053. PMID: 28292938, PMCID: PMC5457712, DOI: 10.1158/1535-7163.mct-16-0794.Peer-Reviewed Original ResearchAdenosine TriphosphateAnimalsAntineoplastic AgentsApoptosisCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationDNA DamageDose-Response Relationship, DrugDrug CombinationsDrug Screening Assays, AntitumorDrug SynergismHigh-Throughput Nucleotide SequencingHumansMiceMitochondriaMolecular Targeted TherapyNeoplastic Stem CellsPancreatic NeoplasmsSuperoxidesXenograft Model Antitumor AssaysSystematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer
Wali VB, Langdon CG, Held MA, Platt JT, Patwardhan GA, Safonov A, Aktas B, Pusztai L, Stern DF, Hatzis C. Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer. Cancer Research 2017, 77: 566-578. PMID: 27872098, PMCID: PMC5582957, DOI: 10.1158/0008-5472.can-16-1901.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTNBC cell linesPairwise drug combinationsClinical translationAggressive diseaseCombination therapyBreast cancerPreclinical proofDrug combinationsCombination treatmentInvestigational drugsSingle agentSensitivity patternCell sensitivityCell linesTherapyApoptotic activityAnticancer activityDownregulated genesMitogenic signalingCrizotinibBlockadeClinicAgentsCancerA Computational Approach for Identifying Synergistic Drug Combinations
Gayvert KM, Aly O, Platt J, Bosenberg MW, Stern DF, Elemento O. A Computational Approach for Identifying Synergistic Drug Combinations. PLOS Computational Biology 2017, 13: e1005308. PMID: 28085880, PMCID: PMC5234777, DOI: 10.1371/journal.pcbi.1005308.Peer-Reviewed Original Research
2015
SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells
Langdon CG, Wiedemann N, Held MA, Mamillapalli R, Iyidogan P, Theodosakis N, Platt JT, Levy F, Vuagniaux G, Wang S, Bosenberg MW, Stern DF. SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells. Oncotarget 2015, 6: 37410-37425. PMID: 26485762, PMCID: PMC4741938, DOI: 10.18632/oncotarget.6138.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisApoptosis Regulatory ProteinsAzepinesAzocinesBenzhydryl CompoundsCamptothecinCell Line, TumorCell ProliferationDocetaxelDose-Response Relationship, DrugDrug SynergismFemaleHumansIrinotecanLung NeoplasmsMice, Inbred BALB CMice, NudeNF-kappa BPaclitaxelSignal TransductionTaxoidsTime FactorsTopoisomerase InhibitorsTriazolesTumor BurdenXenograft Model Antitumor AssaysConceptsLung adenocarcinoma cellsDebio 1143Adenocarcinoma cellsOngoing clinical trialsNon-canonical NF-κB signalingTopoisomerase inhibitorsLung adenocarcinoma xenograftsNF-κB signalingBromodomain inhibitor JQ1Clinical trialsConventional chemotherapyTumor volumeVivo treatmentAdenocarcinoma xenograftsAnti-apoptotic proteinsSingle agentCaspase-8 expressionVivo growthInhibitor JQ1Tumor cellsPro-apoptotic protein SmacJQ1Cell linesInhibitorsTaxanesThe broad‐spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth of BRAF‐mutant melanoma cells in combination with other signaling pathway inhibitors
Langdon CG, Held MA, Platt JT, Meeth K, Iyidogan P, Mamillapalli R, Koo AB, Klein M, Liu Z, Bosenberg MW, Stern DF. The broad‐spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth of BRAF‐mutant melanoma cells in combination with other signaling pathway inhibitors. Pigment Cell & Melanoma Research 2015, 28: 417-430. PMID: 25854919, PMCID: PMC5215495, DOI: 10.1111/pcmr.12376.Peer-Reviewed Original ResearchConceptsBRAF-mutant melanomaBRAF inhibitorsCell linesCombination of dovitinibBRAF inhibitor treatmentBRAF mutant melanoma cellsBRAF inhibitor resistanceColorectal carcinoma cell linesBRAF-mutant melanoma cell linesMelanoma cell linesCarcinoma cell linesMetastatic melanomaEffective therapyWild-type BRAF cellsInhibitor treatmentAgent inhibitsPathway inhibitorDovitinibInhibitor resistanceMelanoma cellsMelanomaSecond agentInhibitorsTreatment