Emerging therapeutic targets for neuroblastoma

Abstract

Introduction: Neuroblastoma (NB) is the prime cancer of infancy, and accounts for 9% of pediatric cancer deaths. While children diagnosed with clinically stable NB experience a complete cure, those with high-risk disease (HR-NB) do not recover, despite intensive therapeutic strategies. Development of novel and effective targeted therapies is needed to counter disease progression, and to benefit long-term survival of children with HR-NB. Areas covered:Recent studies (2017-2020) pertinent to NB evolution are selectively reviewed to recognize novel and effective therapeutic targets. The prospective and promising therapeutic targets/strategies for HR-NB are categorized into (a) targeting oncogene-like and/or reinforcing tumor suppressor (TS)-like lncRNAs; (b) targeting oncogene-like microRNAs (miRs) and/or mimicking TS-miRs; (c) targets for immunotherapy; (d) targeting epithelial-to-mesenchymal transition and cancer stem cells; (e) novel and beneficial combination approaches; and (f) repurposing drugs and other strategies in development.Expert opinion: It is highly unlikely that agents targeting a single candidate or signaling will be beneficial for an HR-NB cure. We must develop efficient drug deliverables for functional targets, which could be integrated and advance clinical therapy. Fittingly, the looming evidence indicated an aggressive evolution of promising novel and integrative targets, development of efficient drugs, and improvised strategies for HR-NB treatment.

Emerging Role and Mechanism of circRNAs in Pediatric Malignant Solid Tumors

“…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 ). Children with high-risk NB remain refractory to cure after multiple intensive treatments, and more than 50% of children relapse, with a 5-year survival rate of approximately 40–50% ( Brignole et al, 2021 ).…”

Chemoprevention of neuroblastoma: progress and promise beyond uncertainties

“…It is the most common cancer in infancy and accounts for about 10% of all childhood cancer deaths worldwide. During embryogenesis, the accumulation of several mutations and molecular rearrangements in sympathoadrenal lineage-committed neural crest cells drives neuroblastoma development [1] . Only 1%-2% of neuroblastoma is inherited (familial neuroblastoma) with a genetic predisposition in a locus mapped to the short arm of Chr16; familial neuroblastoma presents with multifocal primary tumors.…”

LncRNAs and CircRNAs in cancer

“… 40 Based on these mechanistic studies, developing drugs targeting these new biomarkers are popular research directions for cancer treatment. 40 With the various functions and mechanisms in cancer (progression, development, induced therapy resistance, and dissemination), lncRNAs and circRNAs have high value in clinical use in cancer. In our review, we introduce the important roles of lncRNAs and circRNAs in some representative cancers, respectively.…”

“…In recent years, the important functions of identifying new biomarkers in tumors have been continuously studied and revealed, such as the role of new molecular targets in the occurrence and development of tumor cells, the important signaling pathways involved, and their clinical significance in diagnosis and prognosis 40 . Based on these mechanistic studies, developing drugs targeting these new biomarkers are popular research directions for cancer treatment 40 . With the various functions and mechanisms in cancer (progression, development, induced therapy resistance, and dissemination), lncRNAs and circRNAs have high value in clinical use in cancer.…”