MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment

SIMPLE SUMMARY: Neuroblastoma is one of the most diffuse and the deadliest cancer in children. While many advances have been made in the last few decades to improve patients’ outcome, high-risk neuroblastoma (HR-NB) still shows a very aggressive pattern of development and poor prognosis, with only a 50% chance of 5-year survival. Moreover, while many factors contribute to defining the high-risk condition, MYCN status is well established as the major element in pathology disclosure. The aim of this review is to describe the current knowledge in the diagnosis, prognosis and therapeutic approaches of HR-NB, particularly in relation to MYCN. The review highlights how MYCN influences the HR-NB scenario and the new therapeutic approaches that are currently proposed to target it, in consideration of MYCN as a highly relevant target for HR-NB patient management. ABSTRACT: Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features. New and improved therapies have been developed; nevertheless, low efficacy and high toxicity remain a staple feature of current high-risk neuroblastoma treatment. For this reason, more specific procedures are required, and new therapeutic targets are also needed for a precise medicine approach. In this scenario, MYCN is certainly one of the most interesting targets. Indeed, MYCN is one of the most relevant hallmarks of HR-NB, and many studies has been carried out in recent years to discover potent and specific inhibitors to block its activities and any related oncogenic function. N-Myc protein has been considered an undruggable target for a long time. Thus, many new indirect and direct approaches have been discovered and preclinically evaluated for the interaction with MYCN and its pathways; a few of the most promising approaches are nearing clinical application for the investigation in HR-NB.