The quest to develop an effective therapy for neuroblastoma

Abstract

Neuroblastoma (NB) is a common solid extracranial tumor developing in pediatric populations. NB can spontaneously regress or grow and metastasize displaying resistance to therapy. This tumor is derived from primitive cells, mainly those of the neural crest, in the sympathetic nervous system and usually develops in the adrenal medulla and paraspinal ganglia. Our understanding of the molecular characteristics of human NBs continues to advance documenting abnormalities at the genome, epigenome, and transcriptome levels. The high-risk tumors have MYCN oncogene amplification, and the MYCN transcriptional regulator encoded by the MYCN oncogene is highly expressed in the neural crest. Studies on the biology of NB has enabled a more precise risk stratification strategy and a concomitant reduction in the required treatment in an expanding number of cases worldwide. However, newer treatment strategies are mandated to improve outcomes in pediatric patients who are at high-risk and display relapse. To improve outcomes and survival rates in such high-risk patients, it is necessary to use a multicomponent therapeutic approach. Accuracy in clinical staging of the disease and assessment of the associated risks based on biological, clinical, surgical, and pathological criteria are of paramount importance for prognosis and to effectively plan therapeutic approaches. This review discusses the staging of NB and the biological and genetic features of the disease and several current therapies including targeted delivery of chemotherapy, novel radiation therapy, and immunotherapy for NB.

Downregulation of MEG3 and upregulation of EZH2 cooperatively promote neuroblastoma progression

“…Although the outcomes of NB have improved owing to updated and effective interventions, long‐term survival rates in children with high‐risk NB remain relatively poor 1,5 . Accumulating studies on the mechanisms underlying pathogenesis suggest that abnormalities at the genome, epigenome and transcriptome levels are involved in the occurrence of NB 6‐8 . However, our understanding of the complex pathogenic pathways underlying tumorigenesis of NB is still evolving and further research is required for effective diagnosis and identification of therapeutic targets.…”

Emerging Role and Mechanism of circRNAs in Pediatric Malignant Solid Tumors

“…Thirty percent of NB tumors occur in the adrenal medulla, about 60% in the abdominal paravertebral ganglia, and the rest in the sympathetic ganglia of the chest, head, neck, and pelvis ( Rozen and Shohet, 2021 ). Currently, many new targeted therapies and immunotherapies have emerged in addition to conventional radiotherapy for NB ( Blavier et al, 2020 ; Bhoopathi et al, 2021 ; Stainczyk and Westermann, 2021 ). NB is heterogeneous, and approximately 85–90% of children with low- and intermediate-risk NB can be cured, while the survival rate of children with high-risk NB is less than 50% ( Aravindan et al, 2020 ; Quinn et al, 2021 ).…”

Genetic Profiles of Ferroptosis in Malignant Brain Tumors and Off-Target Effects of Ferroptosis Induction

“…Expanding on the treatment boosting effects of ferroptosis induction in glioma, there are also promising findings in other types of cancer. Neuroblastoma is a highly relevant pediatric cancer in younger children ( 11 ), with limited treatment options and therapy resistance if occurring in its high–risk form ( 12 ). Induction of ferroptosis to limit tumor growth has been emerging as a striking new concept to treat neuroblastoma.…”