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

• Published in: Frontiers in endocrinology (Lausanne) Vol. 14; p. 1022192
• Main Authors: Bechmann, Nicole, Westermann, Frank, Eisenhofer, Graeme
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08.06.2023
• Subjects: Adrenal Gland Neoplasms - metabolism; Carcinogenesis - metabolism; catecholamines; Child; Endocrinology; Humans; hypoxia; MYC; Neural Crest - metabolism; Neural Crest - pathology; neuroblastoma; Neuroblastoma - metabolism; pheochromocytoma; Proto-Oncogene Proteins c-myc - metabolism; Signal Transduction - genetics; sympathoadrenal cell lineage; hypoxia; catecholamines; sympathoadrenal cell lineage; MYC; neural crest; neuroblastoma; pheochromocytoma; paraganglioma
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2023.1022192

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 HIF2α appears to contribute to a more aggressive and undifferentiated phenotype in both adrenal neoplasms, whereas 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.