Evolving treatments in high-risk neuroblastoma

ABSTRACT Introduction: Neuroblastoma is a tumor of the developing sympathetic nervous system. Low and intermediate-risk patients usually have good treatment outcomes, whereas high-risk cases have poorer survival and recurrence rates. This review highlights limitations in the treatment procedure and future therapies in development that may be adopted into clinical practice, compiled from a literature search of scientific papers from the last 30 years including ongoing clinical trials. Areas covered: Current treatments for high-risk neuroblastoma have shown efficacy in clinical trials; however, this regimen is not effective in preventing relapse in many cases and has high toxicity for pediatric patients. The two main areas of research for new maintenance therapies focus on immunotherapy and gene targeting with molecular therapy. GD2-CAR-T cells and GD2 vaccines have shown efficacy in pre-clinical trials, and MYCN and ALK inhibition target two of the main driver mutations in neuroblastoma potentially offering a highly specific form of therapy. Expert opinion: Tumor heterogeneity leads to various drivers of neuroblastoma; therefore, combinations of molecular therapies can induce remission, alongside immunotherapy that could lower treatment toxicity. The implementation of ‘liquid biopsies’ could greatly improve genetic characterization of a changing tumor profile (often changing in response to treatment) to inform appropriate therapies.