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.

Release of mitochondrial proteins such as cytochrome c, AIF, Smac/Diablo etc., plays a crucial role in apoptosis induction. A redox‐silent analog of vitamin E, α‐tocopheryl succinate (α‐TOS), was shown to stimulate cytochrome c release via production of reactive oxygen species (ROS) and Bax‐mediated permeabilization of the outer mitochondrial membrane. Here we show that α‐TOS facilitates mitochondrial permeability transition (MPT) in isolated rat liver mitochondria, Tet21N neuroblastoma cells and Jurkat T‐lymphocytes. In particular, in addition to ROS production, α‐TOS stimulates rapid Ca²⁺ entry into the cells with subsequent accumulation of Ca²⁺ in mitochondria—a prerequisite step for MPT induction. Alteration of mitochondrial Ca²⁺ buffering capacity was observed as early as 8 hr after incubation with α‐TOS, when no activation of Bax was yet detected. Ca²⁺ accumulation in mitochondria was important for apoptosis progression, since inhibition of mitochondrial Ca²⁺ uptake significantly mitigated the apoptotic response. Importantly, Ca²⁺‐induced mitochondrial destabilization might cooperate with Bax‐mediated mitochondrial outer membrane permeabilization to induce cytochrome c release from mitochondria.

During the last years, there have been a number of reports that prove involvement of mitochondria in the pathogenesis of variety of disorders including cancer and neurodegenerative diseases. Alteration of vital mitochondrial functions - production of ATP, calcium buffering capacity, abnormal production of reactive oxygen species, can be potentially responsible for pathogenesis of cancer and neurodegenerative diseases. Involvement of mitochondria in various types of cell death makes them attractive targets for tumor cell elimination. This review describes the role of mitochondria in tumor cells and how targeting of mitochondria can be used as a tool in fighting cancer.