Urologic Oncology Branch, National Cancer Institute, National Institutes of Health.
Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Pediatr. 2020 Feb;32(1):26-34. doi: 10.1097/MOP.0000000000000853.
In an attempt to identify potential new therapeutic targets, efforts to describe the metabolic features unique to cancer cells are increasingly being reported. Although current standard of care regimens for several pediatric malignancies incorporate agents that target tumor metabolism, these drugs have been part of the therapeutic landscape for decades. More recent research has focused on the identification and targeting of new metabolic vulnerabilities in pediatric cancers. The purpose of this review is to describe the most recent translational findings in the metabolic targeting of pediatric malignancies.
Across multiple pediatric cancer types, dependencies on a number of key metabolic pathways have emerged through study of patient tissue samples and preclinical modeling. Among the potentially targetable vulnerabilities are glucose metabolism via glycolysis, oxidative phosphorylation, amino acid and polyamine metabolism, and NAD metabolism. Although few agents have yet to move forward into clinical trials for pediatric cancer patients, the robust and promising preclinical data that have been generated suggest that future clinical trials should rationally test metabolically targeted agents for relevant disease populations.
Recent advances in our understanding of the metabolic dependencies of pediatric cancers represent a source of potential new therapeutic opportunities for these diseases.
为了寻找潜在的新治疗靶点,越来越多的研究致力于描述癌细胞特有的代谢特征。虽然目前几种儿科恶性肿瘤的标准治疗方案中包含了针对肿瘤代谢的药物,但这些药物已经存在了几十年。最近的研究集中在识别和靶向儿科癌症中的新代谢脆弱性。本综述旨在描述儿科恶性肿瘤代谢靶向治疗的最新转化研究结果。
通过对患者组织样本和临床前模型的研究,多种儿科癌症类型中出现了对一些关键代谢途径的依赖性。潜在的可靶向弱点包括糖酵解、氧化磷酸化、氨基酸和多胺代谢以及 NAD 代谢途径中的葡萄糖代谢。尽管很少有药物能够进一步进入儿科癌症患者的临床试验,但已经产生的强有力的、有前景的临床前数据表明,未来的临床试验应该合理地测试针对相关疾病人群的代谢靶向药物。
我们对儿科癌症代谢依赖性的理解的最新进展为这些疾病提供了潜在的新治疗机会。