Preclinical models for neuroblastoma: Advances and challenges

Neuroblastoma is a paediatric cancer of the sympathetic nervous system and the most common solid tumour of infancy, contributing to 15% of paediatric oncology deaths. Current therapies are not effective in the long-term treatment of almost 80% of patients with this clinically aggressive disease. The primary challenge in the identification and validation of new agents for paediatric drug development is the accurate representation of tumour biology and diversity. In addition to this limitation, the low incidence of neuroblastoma makes the recruitment of eligible patients for early phase clinical trials highly challenging and highlights the need for robust preclinical testing to ensure that the best treatments are selected. The research field requires new preclinical models, technologies, and concepts to tackle these problems. Tissue engineering offers attractive tools to assist in the development of three-dimensional (3D) cell models using various biomaterials and manufacturing approaches that recreate the geometry, mechanics, heterogeneity, metabolic gradients, and cell communication of the native tumour microenvironment. In this review, we discuss current experimental models and assess their abilities to reflect the structural organisation and physiological conditions of the human body, in addition to current and new techniques to recapitulate the tumour niche using tissue-engineered platforms. Finally, we will discuss the possible use of novel 3D in vitro culture systems to address open questions in neuroblastoma biology.