Cell death-based treatment of neuroblastoma

Neuroblastoma (NB) is the most common solid childhood tumor outside the brain and causes 15% of childhood cancer-related mortality. The main drivers of NB formation are neural crest cell-derived sympathoadrenal cells that undergo abnormal genetic arrangements. Moreover, NB is a complex disease that has high heterogeneity and is therefore difficult to target for successful therapy. Thus, a better understanding of NB development helps to improve treatment and increase the survival rate. One of the major causes of sporadic NB is known to be MYCN amplification and mutations in ALK (anaplastic lymphoma kinase) are responsible for familial NB. Many other genetic abnormalities can be found; however, they are not considered as driver mutations, rather they support tumor aggressiveness. Tumor cell elimination via cell death is widely accepted as a successful technique. Therefore, in this review, we provide a thorough overview of how different modes of cell death and treatment strategies, such as immunotherapy or spontaneous regression, are or can be applied for NB elimination. In addition, several currently used and innovative approaches and their suitability for clinical testing and usage will be discussed. Moreover, significant attention will be given to combined therapies that show more effective results with fewer side effects than drugs targeting only one specific protein or pathway.