Bansal Mohit, Gupta Anamika, Ding Han-Fei
Division of Molecular and Cellular Pathology, Department of Pathology, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Cancers (Basel). 2022 Aug 25;14(17):4113. doi: 10.3390/cancers14174113.
Neuroblastoma is a pediatric cancer responsible for approximately 15% of all childhood cancer deaths. Aberrant MYCN activation, as a result of genomic amplification, is a major driver of high-risk neuroblastoma, which has an overall survival rate of less than 50%, despite the best treatments currently available. Metabolic reprogramming is an integral part of the growth-promoting program driven by MYCN, which fuels cell growth and proliferation by increasing the uptake and catabolism of nutrients, biosynthesis of macromolecules, and production of energy. This reprogramming process also generates metabolic vulnerabilities that can be exploited for therapy. In this review, we present our current understanding of metabolic reprogramming in neuroblastoma, focusing on transcriptional regulation as a key mechanism in driving the reprogramming process. We also highlight some important areas that need to be explored for the successful development of metabolism-based therapy against high-risk neuroblastoma.
神经母细胞瘤是一种儿科癌症，约占所有儿童癌症死亡病例的15%。由于基因组扩增导致的MYCN异常激活是高危神经母细胞瘤的主要驱动因素，尽管目前有最佳治疗方案，但高危神经母细胞瘤的总生存率仍低于50%。代谢重编程是由MYCN驱动的促进生长程序的一个组成部分，它通过增加营养物质的摄取和分解代谢、大分子的生物合成以及能量的产生来推动细胞生长和增殖。这种重编程过程还产生了可用于治疗的代谢脆弱性。在这篇综述中，我们阐述了目前对神经母细胞瘤中代谢重编程的理解，重点关注转录调控作为驱动重编程过程的关键机制。我们还强调了一些重要领域，为成功开发针对高危神经母细胞瘤的基于代谢的疗法，这些领域有待探索。
