Latest advances in cell-death pathway approaches in treating high-risk neuroblastoma

Abstract

Neuroblastoma (NB) is one of childhood's most common malignant tumours worldwide. Upon diagnosis, NB is categorized according to staging and risk, with treatment according to different risk categories. High-risk NB is treated with intensive chemotherapy, surgery, radiation therapy, bone marrow / hematopoietic stem cell transplantation, differentiation treatment of isotretinoin and antibody therapy that is usually administered with the cytokines GM-CSF and IL-2. To date, the genetic profile of NB is still being investigated. The most established gene associated with NB is the MYCN Proto-Oncogene, BHLH Transcription Factor (MYCN) amplification that contributes to the risk stratification of the disease. MYCN gene is an important foetal oncogene involved in cell proliferation for organ and tissue growth. Unfortunately, despite significant advances in the treatment of NB in recent decades, the prognosis for high-risk patients remains unfavourable since the overall 5-year survival rate, according to statistical data, does not exceed 40%. The use of cell technologies in paediatric oncology and haematology occupies a significant place and continues to improve. Since one of the leading causes of tumour development is an imbalance between cell death and cell survival, this paper aims to discuss treatment strategies to eliminate tumour cells using cell death pathways, including inducing apoptosis, necroptosis, autophagy, bioenergetics pathways, and immunotherapy.  In conclusion, there is a need for a well-studied genetic profile of NB, which will allow the identification of new biomarkers, thereby contributing to the development of new therapeutic strategies. At the point of this review, immunotherapy seems to be the most promising treatment for high-risk NB as it has been highly effective in other kinds of cancer.