Current status and future prospects for basic and translational neuroblastoma research

Abstract

The prognosis remains poor for high-risk patients with neuroblastoma (NB) (older age at disease onset, distant metastases, MYCN amplification, telomere abnormalities, and recurrent cases), and only anti-GD2 antibodies have been recently introduced into clinical practice for the treatment of NB since the 1980s. The development of new therapies such as molecular targeted therapies, immunotherapy, and radiation therapy for high-risk groups with NB is still eagerly awaited. In this review, I will update the status of identifying poor prog­nostic biomarker molecules for NB and the development of targeted therapies against these molecules. The biomarkers of poor prognosis in NB and the development of new therapies targeting them include: 1. telomere abnormalities: TERT and ATRX mutations (ATM inhibitors); 2. epigenome abnormalities (EZH1/2 and DNMT inhibitors); 3. MYCN amplification (Aurora-A, CDK7, BRD, and BET inhibitors); 4. cell cycle pathway abnormalities (CDK4/6 and WEE1 inhibitors); 5. RAS/RAF/MAPK pathway abnormalities (MEK inhibitors); and 6. the ATM/ATR/ARF/MDM2/p53 pathway (CHK1 and MDM2 inhibitors). The molecular mechanisms and current status of drug development and clinical trials will be reviewed.