HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics

Pediatric neural crest-derived adrenal neoplasms include neuroblastoma and pheochromocytoma. Both entities are associated with a high degree of clinical heterogeneity, varying from spontaneous regression to malignant disease with poor outcome. Increased expression and stabilization of HIF2 & alpha; appears to contribute to a more aggressive and undifferentiated phenotype in both adrenal neoplasms, whereas MYCN amplification is a valuable prognostic marker in neuroblastoma. The present review focuses on HIF- and MYC signaling in both neoplasms and discusses the interaction of associated pathways during neural crest and adrenal development as well as potential consequences on tumorigenesis. Emerging single-cell methods together with epigenetic and transcriptomic analyses provide further insights into the importance of a tight regulation of HIF and MYC signaling pathways during adrenal development and tumorigenesis. In this context, increased attention to HIF-MYC/MAX interactions may also provide new therapeutic options for these pediatric adrenal neoplasms.

Automated summary

Pediatric neural crest-derived adrenal neoplasms, such as neuroblastoma and pheochromocytoma, exhibit clinical heterogeneity with varying outcomes. Increased HIF2α expression and MYCN amplification contribute to aggressiveness and poor prognosis. Understanding HIF and MYC signaling pathways can provide insights into tumorigenesis and potential therapeutic targets for these pediatric adrenal neoplasms.