Developing preclinical models of neuroblastoma: driving therapeutic testing

Despite advances in cancer therapeutics, particularly in the area of immuno-oncology, successful treatment of neuroblastoma (NB) remains a challenge. NB is the most common cancer in infants under 1 year of age, and accounts for approximately 10% of all pediatric cancers. Currently, children with high-risk NB exhibit a survival rate of 40–50%. The heterogeneous nature of NB makes development of effective therapeutic strategies challenging. Many preclinical models attempt to mimic the tumor phenotype and tumor microenvironment. In vivo mouse models, in the form of genetic, syngeneic, and xenograft mice, are advantageous as they replicated the complex tumor-stroma interactions and represent the gold standard for preclinical therapeutic testing. Traditional in vitro models, while high throughput, exhibit many limitations. The emergence of new tissue engineered models has the potential to bridge the gap between in vitro and in vivo models for therapeutic testing. Therapeutics continue to evolve from traditional cytotoxic chemotherapies to biologically targeted therapies. These therapeutics act on both the tumor cells and other cells within the tumor microenvironment, making development of preclinical models that accurately reflect tumor heterogeneity more important than ever. In this review, we will discuss current in vitro and in vivo preclinical testing models, and their potential applications to therapeutic development.