2023
Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma
Berko E, Witek G, Matkar S, Petrova Z, Wu M, Smith C, Daniels A, Kalna J, Kennedy A, Gostuski I, Casey C, Krytska K, Gerelus M, Pavlick D, Ghazarian S, Park J, Marachelian A, Maris J, Goldsmith K, Radhakrishnan R, Lemmon M, Mossé Y. Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma. Nature Communications 2023, 14: 2601. PMID: 37147298, PMCID: PMC10163008, DOI: 10.1038/s41467-023-38195-0.Peer-Reviewed Original ResearchConceptsAnaplastic lymphoma kinaseLorlatinib resistanceTumor DNAPhase 1 trialCirculating tumor DNAPre-clinical studiesResistance mechanismsTumor DNA samplesALK mutationsDisease progressionHeterogeneity of tumorsClinical utilityRAS-MAPK pathwayTherapeutic strategiesLymphoma kinasePatientsResistance mutationsNeuroblastomaProgressionTrialsMutationsBiochemical assaysDNA samplesPoint mutationsLorlatinib
2019
Computational algorithms for in silico profiling of activating mutations in cancer
Jordan EJ, Patil K, Suresh K, Park JH, Mosse YP, Lemmon MA, Radhakrishnan R. Computational algorithms for in silico profiling of activating mutations in cancer. Cellular And Molecular Life Sciences 2019, 76: 2663-2679. PMID: 30982079, PMCID: PMC6589134, DOI: 10.1007/s00018-019-03097-2.Peer-Reviewed Original ResearchConceptsTarget proteinsSingle nucleotide polymorphismsB-RafSerine/threonine-protein kinase B-RafDifferent target proteinsEffects of mutationsStructure-based computational approachKinase domainStructure-based methodsStructure-based modelProtein structureProtein activationSilico profilingAnaplastic lymphoma kinaseInteraction of inhibitorsMutational landscapeHuman cancersPoint mutationsProteinMutationsMutational patternsDifferent mutationsActivation statusComputational approachLymphoma kinase
2016
The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma
Infarinato NR, Park JH, Krytska K, Ryles HT, Sano R, Szigety KM, Li Y, Zou HY, Lee NV, Smeal T, Lemmon MA, Mossé YP. The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Cancer Discovery 2016, 6: 96-107. PMID: 26554404, PMCID: PMC4707106, DOI: 10.1158/2159-8290.cd-15-1056.Peer-Reviewed Original ResearchMeSH KeywordsAminopyridinesAnaplastic Lymphoma KinaseAnimalsCell Line, TumorCrizotinibDrug Resistance, NeoplasmHumansLactamsLactams, MacrocyclicMiceMutationNeuroblastomaPhosphorylationProtein Kinase InhibitorsPyrazolesPyridinesReceptor Protein-Tyrosine KinasesTreatment OutcomeXenograft Model Antitumor AssaysConceptsAnaplastic lymphoma kinaseCrizotinib resistancePF-06463922ALK variantsTreatment of patientsALK inhibitor crizotinibPatient-derived xenograftsXenograft mouse modelPreclinical rationaleClinical obstacleNeuroblastoma modelClinical trialsTumor regressionPrimary resistanceInhibitor crizotinibXenograft tumorsMouse modelXenograft modelLymphoma kinaseNeuroblastomaCrizotinibHigh potencyF1174LVivo dataImproved potency
2012
Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma
Carpenter EL, Haglund EA, Mace EM, Deng D, Martinez D, Wood AC, Chow AK, Weiser DA, Belcastro LT, Winter C, Bresler SC, Asgharzadeh S, Seeger R, Zhao H, Guo R, Christensen J, Orange J, Pawel B, Lemmon M, Mossé Y. Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma. Oncogene 2012, 31: 4859-4867. PMID: 22266870, PMCID: PMC3730824, DOI: 10.1038/onc.2011.647.Peer-Reviewed Original ResearchMeSH KeywordsAnaplastic Lymphoma KinaseAntibodies, MonoclonalAntigens, NeoplasmCell DeathCell Line, TumorCell ProliferationCrizotinibHumansMutationNeuroblastomaPhosphorylationProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins c-metPyrazolesPyridinesReceptor Protein-Tyrosine KinasesSignal TransductionConceptsAnaplastic lymphoma kinaseLymphoma kinaseHuman neuroblastomaSmall molecule tyrosine kinase inhibitorsAntibody-dependent cellular cytotoxicityReceptor tyrosine kinasesDevastating pediatric cancerSympathetic nervous systemALK inhibitor crizotinibComplementary therapeutic approachALK-positive tumorsPromising therapeutic strategyTyrosine kinase inhibitorsAntibody-induced growth inhibitionCell linesTractable therapeutic targetWild-type ALKTyrosine kinaseALK aberrationsNeuroblastoma patientsLung cancerALK mutationsInhibitor crizotinibCellular cytotoxicityALK antibody