Abstract
Neuroblastoma is a type of cancer intimately related with early development and differentiation of neuroendocrine cells, and constitutes one of the pediatric cancers with higher incidence and mortality. Protein tyrosine phosphatases (PTPs) are key regulators of cell growth and differentiation by their direct effect on tyrosine dephosphorylation of specific protein substrates, exerting major functions in the modulation of intracellular signaling during neuron development in response to external cues driving cell proliferation, survival, and differentiation. We review here the current knowledge on the role of PTPs in neuroblastoma cell growth, survival, and differentiation. The potential of PTPs as biomarkers and molecular targets for inhibition in neuroblastoma therapies is discussed.
Highlights
Neuroblastoma is the most common extracranial solid tumor diagnosed in infants and the paediatric cancer with higher risk of death, with high-risk neuroblastoma showing a survival rate of about 50% (Ward et al, 2014; Siegel et al, 2020)
The involvement of Protein tyrosine phosphatases (PTPs) in the regulation of neuroblastoma cell signaling and development mediated by the distinct receptor tyrosine kinases (RTKs)/MYCN
Axes argues for PTPs as relevant biomarkers and potential therapeutic targets in this type of cancer. This is reinforced by the differential association found between neuroblastoma patient outcome and expression of specific PTP genes in neuroblastoma tumor samples, as illustrated along this review
Summary
Neuroblastoma is the most common extracranial solid tumor diagnosed in infants and the paediatric cancer with higher risk of death, with high-risk neuroblastoma (about 50% of neuroblastoma cases) showing a survival rate of about 50% (Ward et al, 2014; Siegel et al, 2020). Neuroblastoma tumors arise from endocrine neural crest precursor cells during aberrant development of sympathetic neuronal cells early in life This makes neuroblastoma potentially actionable from the perspective of the developmental biology of neuroendocrine cells (Cheung and Dyer, 2013; Fletcher et al, 2018). The low number of mutations found in neuroblastoma tumors at diagnosis, their high diversity, and the paediatric nature of the patients, have been handicaps for the identification and validation of actionable molecular targets. In this context, anti-disialoganglioside GD2 monoclonal antibody immunotherapy is the only current targeted therapy for high-risk neuroblastoma (Pastor and Mousa, 2019; Moreno et al, 2020). Insights are made on specific PTPs as potential neuroblastoma biomarkers and molecular therapeutic targets
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