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dc.contributor.authorGomez, Roshna Lawrence
dc.contributor.authorAli, Fahad R.
dc.date.accessioned2023-12-18T07:31:43Z
dc.date.available2023-12-18T07:31:43Z
dc.date.issued2023
dc.identifier.other204-2023.139
dc.identifier.urihttps://repository.mbru.ac.ae/handle/1/1399
dc.description.abstractAbstract: Neuroblastoma is the most common extracranial solid tumor in infants, arising from developmentally stalled neural crest-derived cells. Driving tumor differentiation is a promising therapeutic approach for this devastating disease. Here, we show that the CDK4/6 inhibitor palbociclib not only inhibits proliferation but induces extensive neuronal differentiation of adrenergic neuroblastoma cells. Palbociclib-mediated differentiation is manifested by extensive phenotypic and transcriptional changes accompanied by the establishment of an epigenetic program driving expression of mature neuronal features. In vivo palbociclib significantly inhibits tumor growth in mouse neuroblastoma models. Furthermore, dual treatment with retinoic acid resets the oncogenic adrenergic core regulatory circuit of neuroblastoma cells, further suppresses proliferation, and can enhance differentiation, altering gene expression in ways that significantly correlate with improved patient survival. We therefore identify palbociclib as a therapeutic approach to dramatically enhance neuroblastoma differentiation efficacy that could be used in combination with retinoic acid to improve patient outcomes.en_US
dc.language.isoenen_US
dc.subjectPalbocicliben_US
dc.subjectNeuroblastomaen_US
dc.subjectLatent Differentiation Capacityen_US
dc.titlePalbociclib releases the latent differentiation capacity of neuroblastoma cellsen_US
dc.typeArticleen_US


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