Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice
Huang KM, Leblanc AF, Uddin ME, Kim JY, Chen M, Eisenmann ED, Gibson A, Li Y, Hong KW, DiGiacomo D, Xia S, Alberti P, Chiorazzi A, Housley SN, Cope TC, Sprowl JA, Wang J, Loprinzi CL, Noonan A, Lustberg M, Cavaletti G, Pabla N, Hu S, Sparreboom A. Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice. Journal Of Clinical Investigation 2020, 130: 4601-4606. PMID: 32484793, PMCID: PMC7456253, DOI: 10.1172/jci136796.Peer-Reviewed Original ResearchConceptsOrganic cation transporter 2Peripheral neurotoxicityColorectal cancerOxaliplatin-induced peripheral neurotoxicityOxaliplatin-containing therapyOxaliplatin-induced neurotoxicitySatellite glial cellsOxaliplatin neurotoxicityChronic formCancer patientsGlial cellsPreclinical modelsPreventive strategiesMouse modelPharmacological approachesPharmacological targetingTranslational significanceNeurotoxicityTransporter 2PatientsUptake transportersCancerAnticancer drugsCandidate transportersSolute carriersA phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer receiving FOLFOX chemotherapy and bevacizumab.
Noonan A, Lustberg M, Schnell P, Hays J, Jin N, Abushahin L, Malalur P, Roychowdhury S, Elkhatib R, Chen H, Al Mutar S, Sparreboom A, Hu S. A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer receiving FOLFOX chemotherapy and bevacizumab. Journal Of Clinical Oncology 2020, 38: tps12125-tps12125. DOI: 10.1200/jco.2020.38.15_suppl.tps12125.Peer-Reviewed Original ResearchOxaliplatin-induced peripheral neuropathyOxaliplatin-induced neuropathyOrganic cation transporter 2Peripheral neuropathyColorectal cancerChronic oxaliplatin-induced peripheral neuropathyStage IV colorectal cancerRat dorsal root gangliaOxaliplatin-induced neurotoxicityPharmacokinetics of oxaliplatinPhase 2 doseMetastatic colorectal cancerPhase 1b trialDose-finding studyDorsal root gangliaAddition of dasatinibQuality of lifeSmall molecule kinase inhibitorsFOLFOX chemotherapyOral dasatinibBevacizumab therapyRoot gangliaSerum biomarkersIntermittent doseRat modelDifferential Contribution of Neuronal Uptake Transporters to Oxaliplatin Peripheral Neurotoxicity
Huang K, Leblanc A, Alberti P, Sprowl J, Wang J, Lustberg M, Cavaletti G, Hu S, Sparreboom A. Differential Contribution of Neuronal Uptake Transporters to Oxaliplatin Peripheral Neurotoxicity. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.03083.Peer-Reviewed Original ResearchDorsal root gangliaPeripheral neurotoxicityColorectal cancerOxaliplatin-induced peripheral neurotoxicityVon Frey hair testChronic peripheral neurotoxicityOxaliplatin-induced neurotoxicityVivo cultureColorectal cancer cellsWild-type ratsEx vivo cultureOxaliplatin therapyAfford neuroprotectionObserved neuroprotectionNeurological injuryRoot gangliaOxaliplatin accumulationSystemic clearanceConventional chemotherapyGlial cellsPreclinical modelsSprague-DawleySensory neuronsMouse modelSide effects