Neuroblastoma is a devastating pediatric solid tumor that, despite significant recent advances, still accounts for nearly 15% of all childhood cancer deaths. Patients are risk stratified based on a number of features, including amplification of theMYCNoncogene, yet targetingMYCNitself has been unsuccessful to date. The complex interplay between this oncogene and its many metabolic targets has proven challenging and is only beginning to be understood in the context of pediatric tumors. It is increasingly recognized, however, thatMYCN-driven metabolic rewiring and concomitant increases in biosynthetic precursors has the potential to drive many aspects of tumor development. Furthermore, emerging research suggests that improving overall therapeutic outcomes for neuroblastoma patients may well require individual metabolic profiling, allowing personalized simultaneous targeting of multiple metabolic nodes. In this review, we outline clinically relevant research involvingMYCN-driven metabolic derangements, including increased glucose uptake, polyamine synthesis, glycosylation, and others, and attempt to summarize the influence ofMYCNon important metabolic genes and druggable protein targets. We spotlight emerging research in glycosylation and its modulation as an often overlooked but increasingly promising therapeutic area. It is our hope that this document will provide utility for both clinicians and scientists seeking to understand how theMYCNoncogene and metabolism are critically intertwined.
神经母细胞瘤是一种破坏性的儿童实体肿瘤，尽管近期取得显著进展，但仍占所有儿童癌症死亡病例的近15%。患者的风险分层基于多种特征，包括MYCN癌基因的扩增，然而迄今为止针对MYCN本身的治疗尚未成功。该癌基因与其众多代谢靶点之间复杂的相互作用已被证明具有挑战性，且仅在儿童肿瘤背景下开始被理解。然而人们日益认识到，MYCN驱动的代谢重编程及伴随的生物合成前体增加，可能驱动肿瘤发展的多个方面。此外，新兴研究表明，改善神经母细胞瘤患者的总体治疗效果很可能需要个体化代谢谱分析，以实现对多个代谢节点的个性化同步靶向。本综述概述了涉及MYCN驱动代谢紊乱的临床相关研究，包括葡萄糖摄取增加、多胺合成、糖基化等，并尝试总结MYCN对重要代谢基因及可成药蛋白靶点的影响。我们重点关注糖基化及其调控这一常被忽视但日益前景广阔的治疗领域的新兴研究。希望本文能为临床医生和科研人员理解MYCN癌基因与代谢如何紧密交织提供参考价值。
MYCN-Driven Metabolic Networks Are a Critical Dependency of High-Risk Neuroblastomas
肿瘤(癌症)患者之家