Butler Miriam, van der Meer Laurens T, van Leeuwen Frank N
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Laboratory of Pediatric Oncology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Trends Endocrinol Metab. 2021 Jun;32(6):367-381. doi: 10.1016/j.tem.2021.03.003. Epub 2021 Mar 29.
Targeting tumor cell metabolism is an attractive form of therapy, as it may enhance treatment response in therapy resistant cancers as well as mitigate treatment-related toxicities by reducing the need for genotoxic agents. To meet their increased demand for biomass accumulation and energy production and to maintain redox homeostasis, tumor cells undergo profound changes in their metabolism. In addition to the diversion of glucose metabolism, this is achieved by upregulation of amino acid metabolism. Interfering with amino acid availability can be selectively lethal to tumor cells and has proven to be a cancer specific Achilles' heel. Here we review the biology behind such cancer specific amino acid dependencies and discuss how these vulnerabilities can be exploited to improve cancer therapies.
靶向肿瘤细胞代谢是一种颇具吸引力的治疗方式，因为它可能增强对治疗耐药癌症的治疗反应，并通过减少对基因毒性药物的需求来减轻治疗相关毒性。为满足其对生物量积累和能量产生不断增加的需求并维持氧化还原稳态，肿瘤细胞在代谢方面发生了深刻变化。除了葡萄糖代谢的转向外，这还通过上调氨基酸代谢来实现。干扰氨基酸的可用性对肿瘤细胞可能具有选择性致死性，并且已被证明是癌症特有的致命弱点。在此，我们综述此类癌症特异性氨基酸依赖性背后的生物学原理，并讨论如何利用这些弱点来改善癌症治疗。
