Defining neuroblastoma: from origin to precision medicine

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation agents, as well as personalized combinatory therapies as potential approaches for improving the survival and quality of life of children with NB. Graphical Abstract Neuroblastoma is the most common extracranial solid tumor of childhood, and significant progress has been achieved in understanding its origin, biology, and new, more efficient therapies. In this review, we discuss the latest advances in defining the cell of origin, the current treatment protocols, and the precision medicine strategies under development, including metabolism, induction of differentiation, and immunotherapy, as well as the implications of the tumor microenvironment on tumorigenesis and as a treatment target.