Promising Molecular Targets and Novel Therapeutic Approaches in Neuroblastoma

Abstract

Abstract Purpose of Review This article provides a brief and up-to-date overview of promising molecular targets and novel therapeutic approaches in neuroblastoma (NB). Recent Findings High-risk NB is hard to manage with existing treatment modalities, so more than half of those cases are unable to achieve long-term survival. With a deep understanding of molecular pathogenesis, numerous therapeutic targets have been discovered, offering a wide range of novel strategies to treat high-risk NB. Several molecular targets or pathways of NB are well studied, such as GD2, MYCN, ALK, p53/MDM2, PI3K/Akt/mTOR/, and RAS/MAPK signaling. Novel targeted drugs and combined therapies are being developed and investigated for treating high-risk NB in preclinical and clinical trials. Considering different NB patients respond to molecular-guided therapy and conventional therapy differently, how to design an effective personalized therapy remains a big challenge. Summary Anti-GD2 monoclonal antibodies have been approved to treat high-risk NB. Inhibitors targeting MYCN, ALK, p53/MDM2, RAS/MAPK, and PI3K/Akt/mTOR are being tested in phase I/II clinical trials. However, most research on molecularly targeted therapy stays at the preclinical level. More valuable targets need to be identified, and more efficient therapies need to be developed. Further, exploration of new combinations using inhibitors targeting multiple targets and conventional therapy is still the most important research direction in future, which would advance treatment regimens, improve outcomes, and prolong survival in children with high-risk NB.