High-risk neuroblastoma: ATRX and TERT as prognostic markers and therapeutic targets. Review and update on the topic

High-risk neuroblastoma continues to show a very high mortality, with a 5-year survival rate of 50%. While MYCN amplification is the main genetic alteration associated with high-risk tumours, other molecular mechanisms, such as alterations in ATRX and TERT, remain poorly understood.

ATRX and TERT biomarkers, which are associated with a more aggressive neuroblastoma pattern, should be considered for accurate prognostic stratification.

We highlight the promising results of the clinical trial involving the combination of adavosertib and irinotecan, which encourages further clinical trials with adavosertib targeting NB with ATRX mutations. Preclinical results with BET inhibitors (OTX015 and AZD5153) and with 6-thio-2′-deoxyguanosine, targeting NB with TERT mutations, are promising. Both represent future therapeutic targets, emphasizing the need to prioritize research using these models.