Neuroblastoma: Emerging trends in pathogenesis, diagnosis, and therapeutic targets.

Neuroblastoma (NB) accounts for about 13% of all pediatric cancer mortality and is the leading cause of pediatric cancer death for children aged 1 to 5 years. NB, a developmental malignancy of neural ganglia, originates from neural crest-derived cells, which undergo a defective sympathetic neuronal differentiation due to genomic and epigenetic aberrations. NB is a complex disease with remarkable biological and genetic variation and clinical heterogeneity, such as spontaneous regression, treatment resistance, and poor survival rates. Depending on its severity, NB is categorized as high-risk, intermediate-risk, and low-risk., whereas high-risk NB accounts for a high infant mortality rate. Several studies revealed that NB cells suppress immune cell activity through diverse signaling pathways, including exosome-based signaling pathways. Exosome signaling has been shown to modulate gene expression in the target immune cells and attenuate the signaling events through non-coding RNAs. Since high-risk NB is characterized by a low survival rate and high clinical heterogeneity with current intensive therapies, it is crucial to unravel the molecular events of pathogenesis and develop novel therapeutic targets in high-risk, relapsed, or recurrent tumors in NB to improve patient survival. This article discusses etiology, pathophysiology, risk assessment, molecular cytogenetics, and the contribution of extracellular vesicles, non-coding RNAs, and cancer stem cells in the tumorigenesis of NB. We also detail the latest developments in NB immunotherapy and nanoparticle-mediated drug delivery treatment options.