2024
Network-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis
Rosenberger G, Li W, Turunen M, He J, Subramaniam P, Pampou S, Griffin A, Karan C, Kerwin P, Murray D, Honig B, Liu Y, Califano A. Network-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis. Nature Communications 2024, 15: 3909. PMID: 38724493, PMCID: PMC11082183, DOI: 10.1038/s41467-024-47957-3.Peer-Reviewed Original ResearchConceptsMechanism of cell responseResistance mechanismsSignaling pathway responsesDrug resistance mechanismsEnzyme/substrate interactionsAdaptive resistance mechanismsNetwork rewiringPhosphorylation stateSignaling Pathway ActivationDrug perturbationsProteomic technologiesSignaling crosstalkPathway responsesInhibitor designPathway activationCancer drug resistance mechanismsCell adaptive responsesAdaptive responsePhosphatase activityNetwork-based methodologyRewiringTherapeutic efficacyPhosphoproteome coverageCell responsesControl medium
2023
Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis
Sonnenkalb L, Carter J, Spitaleri A, Iqbal Z, Hunt M, Malone K, Utpatel C, Cirillo D, Rodrigues C, Nilgiriwala K, Fowler P, Merker M, Niemann S, Consortium C, Barilar I, Battaglia S, Borroni E, Brandao A, Brankin A, Cabibbe A, Carter J, Cirillo D, Claxton P, Clifton D, Cohen T, Coronel J, Crook D, Dreyer V, Earle S, Escuyer V, Ferrazoli L, Fowler P, Gao G, Gardy J, Gharbia S, Ghisi K, Ghodousi A, Cruz A, Grandjean L, Grazian C, Groenheit R, Guthrie J, He W, Hoffmann H, Hoosdally S, Hunt M, Iqbal Z, Ismail N, Jarrett L, Joseph L, Jou R, Kambli P, Khot R, Knaggs J, Koch A, Kohlerschmidt D, Kouchaki S, Lachapelle A, Lalvani A, Lapierre S, Laurenson I, Letcher B, Lin W, Liu C, Liu D, Malone K, Mandal A, Mansjö M, Matias D, Meintjes G, de Freitas Mendes F, Merker M, Mihalic M, Millard J, Miotto P, Mistry N, Moore D, Musser K, Ngcamu D, Hoang N, Niemann S, Nilgiriwala K, Nimmo C, Okozi N, Oliveira R, Omar S, Paton N, Peto T, Pinhata J, Plesnik S, Puyen Z, Rabodoarivelo M, Rakotosamimanana N, Rancoita P, Rathod P, Rodger G, Rodrigues C, Rodwell T, Roohi E, Santos-Lazaro D, Shah S, Kohl T, Smith G, Solano W, Spitaleri A, Supply P, Surve U, Tahseen S, Thuong N, Thwaites G, Todt K, Trovato A, Utpatel C, Van Rie A, Vijay S, Walker T, Walker S, Warren R, Werngren J, Wijkander M, Wilkinson R, Wilson D, Wintringer P, Yu X, Yang Y, Zhao Y, Yao S, Zhu B. Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis. The Lancet Microbe 2023, 4: e358-e368. PMID: 37003285, PMCID: PMC10156607, DOI: 10.1016/s2666-5247(23)00002-2.Peer-Reviewed Original ResearchConceptsMutation catalogueIn silico data analysisBedaquiline resistanceClofazimine resistanceResistance mechanismsProtein modelsClinical Mycobacterium tuberculosis complex isolatesImpaired DNA bindingClinically resistant strainsMinimum inhibitory concentrationVariants in vitroPacBio sequencingGenome sequenceGenomic rearrangementsGenomic variantsIn vitroExperimental evolutionGenotype dataTranscriptional repressorDrug resistance mechanismsClinical isolatesPhenotypic dataResistance determinantsDNA bindingProtein dimerisation
2022
PROTACs: past, present and future
Li K, Crews CM. PROTACs: past, present and future. Chemical Society Reviews 2022, 51: 5214-5236. PMID: 35671157, PMCID: PMC10237031, DOI: 10.1039/d2cs00193d.Peer-Reviewed Original ResearchConceptsProtein of interestProteolysis-targeting chimerasUbiquitin-proteasome systemE3 ubiquitin ligaseSmall molecule inhibitorsUbiquitin ligaseNonenzymatic functionProtein degradationHeterobifunctional moleculesDrug resistance mechanismsMolecule inhibitorsSubsequent degradationUbiquitinationLigasePromising therapeuticsProteinChimerasPotential toxicityDegradationMechanism
2021
A review of FLT3 inhibitors in acute myeloid leukemia
Zhao JC, Agarwal S, Ahmad H, Amin K, Bewersdorf JP, Zeidan AM. A review of FLT3 inhibitors in acute myeloid leukemia. Blood Reviews 2021, 52: 100905. PMID: 34774343, PMCID: PMC9846716, DOI: 10.1016/j.blre.2021.100905.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaFLT3 mutationsMyeloid leukemiaTreatment of AMLInhibitor maintenance therapyDrug resistance mechanismsCommon genetic aberrationsConsolidation chemotherapyRefractory FLT3Maintenance therapyPoor prognosisPrognostic implicationsStromal protectionFLT3 inhibitorsStandard inductionADMIRAL studyFLT3Genetic aberrationsLeukemiaResistance mechanismsMutationsMonotherapyChemotherapyPrognosisGilteritinib
2018
Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain?
Kabraji S, Ni J, Lin NU, Xie S, Winer EP, Zhao JJ. Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain? Clinical Cancer Research 2018, 24: 1795-1804. PMID: 29437794, PMCID: PMC5899637, DOI: 10.1158/1078-0432.ccr-17-3351.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsAntineoplastic Combined Chemotherapy ProtocolsBlood-Brain BarrierBrain NeoplasmsBreast NeoplasmsClinical Studies as TopicDisease Models, AnimalDrug DevelopmentDrug Evaluation, PreclinicalDrug Resistance, NeoplasmFemaleHumansMiceModels, BiologicalReceptor, ErbB-2Translational Research, BiomedicalTreatment OutcomeXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesHER2-positive breast cancer brain metastasesTreatment of BCBMHER2-positive breast cancerHER2-targeting drugsInadequate drug penetrationBrain metastasis modelCancer brain metastasesCentral nervous systemClin Cancer ResDrug resistance mechanismsBrain metastasesFirst metastasisEffective therapyCommon siteBreast cancerMetastasis modelPharmacodynamic dataNervous systemTranslational research paradigmDrug penetrationCancer ResDrug sensitivityPatientsDrug development
2015
MEK Inhibitor PD-0325901 Overcomes Resistance to CK2 Inhibitor CX-4945 and Exhibits Anti-Tumor Activity in Head and Neck Cancer
Bian Y, Han J, Kannabiran V, Mohan S, Cheng H, Friedman J, Zhang L, VanWaes C, Chen Z. MEK Inhibitor PD-0325901 Overcomes Resistance to CK2 Inhibitor CX-4945 and Exhibits Anti-Tumor Activity in Head and Neck Cancer. International Journal Of Biological Sciences 2015, 11: 411-422. PMID: 25798061, PMCID: PMC4366640, DOI: 10.7150/ijbs.10745.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBlotting, WesternCasein Kinase IICell Line, TumorDiphenylamineFemaleFlow CytometryHead and Neck NeoplasmsHumansJNK Mitogen-Activated Protein KinasesMiceMice, Inbred BALB CMice, SCIDNaphthyridinesNF-kappa BPhenazinesProto-Oncogene Proteins c-fosTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsAnti-tumor activityMEK inhibitor PD-0325901PD-901CK2 inhibitor CXModest anti-tumor activityNeck squamous cell carcinomaPD-0325901Cell linesSignificant anti-tumor effectHuman HNSCC cell linesUM-SCC cell linesP-AKT T308Squamous cell carcinomaIL-8 activityFurther clinical investigationAnti-tumor effectsHNSCC cell linesDNA flow cytometryAP-1 pathwayDrug resistance mechanismsExhibit anti-tumor activityResistance mechanismsUM-SCC1Cell carcinomaNeck cancer
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