Cell death-based treatment of neuroblastoma

Abstract

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.

Gangliosides and Neuroblastomas

“…MYCN (V-myc myelocytomatosis viral-related oncogene, neuroblastoma derived) amplification, associated with spontaneous NB and found in about 20% of all NBs, is associated with a poor prognosis [ 4 , 129 , 130 ]; although children with tumors without MYCN amplification can also do poorly [ 131 , 132 ]. While the prognostic value of MYCN is highly context-dependent [ 133 ], its determination has been recommended as a mandatory step when determining treatment [ 4 , 134 ]. Overexpression of MYCN allows it to form heterodimers with MYC-associated protein X (MAX) which permits it to act as a transcriptional factor and support continued tumor growth [ 135 ].…”

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database

“…Neuroblastoma (NB) stem from the adrenal glands [ 1 ] and appear as a type of extracranial solid tumors occurring in children, which constitute 15% of child deaths from cancers [ 2 3 ], with the incidence rate being 1/7,000–1/8,000. Multimodal therapy currently seems an effective treatment for NB, which includes operation, chemotherapy, radiotherapy and immunotherapy [ 4 5 6 7 8 ]. Generally, children with low-risk NB have a good prognosis and seldom need intensified therapy [ 9 10 11 ], while patients with high-risk NB are diagnosed with obvious tumor progression, showing a bad prognosis, with the long-term survival rate being 50% [ 12 13 ].…”

Necroptosis and Caspase-2-Mediated Apoptosis of Astrocytes and Neurons, but Not Microglia, of Rat Hippocampus and Parenchyma Caused by Angiostrongylus cantonensis Infection

“…The various caspases that are involved in hippocampal and parenchymal apoptosis in permissive hosts (caspase-2, Figures 3-6) and non-permissive hosts (caspase-3 and caspase-6) (Li et al, 2014) upon A. cantonensis infection might help to uncover the underlying mechanism of the distinct pathological outcomes in infected rats and mice. Additionally, novel drugs, such as acetylcysteine, that target apoptosis and necroptosis signaling pathways in combination with anthelmintics may serve as alternative therapies for the treatment of A. cantonensis infection since some of them have been approved by the United States Food and Drug Administration for the treatment of cancer, neuroblastoma and autoimmune and inflammatory diseases (Ocker and Höpfner, 2012;Denisenko et al, 2018;Kaminskyy and Zhivotovsky, 2018;Valter et al, 2018).…”