Neuroblastoma models for insights into tumorigenesis and new therapies.

INTRODUCTION: Neuroblastoma is the most common extracranial solid tumor in children. It occurs in the adrenosympathetic lineage, which is derived from the neural crest. MYCN amplification is found in about 20% of cases and is the most powerful prognostic factor. Anaplastic lymphoma kinase (ALK) mutation is also found in 7% of sporadic neuroblastomas and 50% of familial neuroblastomas. Although several mutations other than ALK are also found, about 70% of neuroblastomas show no mutations. Another important feature of neuroblastoma is that it sometimes spontaneously regresses. These features collectively suggest that neuroblastoma is caused by aberrations in the normal development processes of the neural crest. AREAS COVERED: This review highlights a number of models of neuroblastoma including genetically engineered mouse models (GEMMs). The main GEMMs described here are: tyrosine hydroxylase (TH)-MYCN, TH-MYCN/Trp53(+/-), TH-MYCN/TH-Cre/Casp8(flox/flox), TH-MYCN/TH-ALK(F1174L) and DBH-iCre/CAG-LSL-Lin28b. EXPERT OPINION: The current mouse models available are very useful for investigating the mechanisms of tumorigenesis and for developing therapeutics. However, many aspects have not yet been addressed. These include immediate early events after tumor initiation, epigenetic changes, spontaneous regression and metastasis. On the other hand, the current models do not perfectly recapitulate features of human neuroblastoma. Therefore, humanized mice and new GEMMs should be also considered for future research.