Stalling the engine of resistance: targeting cancer metabolism to overcome therapeutic resistance.
Stalling the engine of resistance: targeting cancer metabolism to overcome therapeutic resistance.
复制标题
DOI：
10.1158/0008-5472.can-12-3009
复制
发表时间：
2013-05-01
期刊：
影响因子：
11.2
通讯作者：
Tan M
中科院分区：
文献类型：
--
作者：
Butler EB;Zhao Y;Muñoz-Pinedo C;Lu J;Tan M
癌细胞与正常细胞在如何利用其代谢途径来促进细胞生长和存活方面有显着不同。通过增加摄取和改变代谢利用来消除这些差异的两种基本代谢物是葡萄糖和谷氨酰胺。这些分子可以被分解代谢以制造活跃细胞生长和增殖所需的许多构件。维持这种生长所必需的代谢途径的改变与治疗抗性有关，这是一种与患者预后不良相关的特征。通过靶向输入、分解代谢和合成必需细胞组分的代谢途径，耐药癌细胞通常可以对抗癌治疗重新敏感。针对癌症代谢的独特方面的药剂的特异性和功效预期是高的;并且当与更传统的治疗剂组合使用时，可以提供克服肿瘤内的抗性的途径，所述肿瘤不再对当前形式的治疗有反应。
Cancer cells are markedly different from normal cells with regards to how their metabolic pathways are utilized to fuel cellular growth and survival. Two basic metabolites that exemplify these differences through increased uptake and altered metabolic usage are glucose and glutamine. These molecules can be catabolized to manufacture many of the building blocks required for active cell growth and proliferation. The alterations in the metabolic pathways necessary to sustain this growth have been linked to therapeutic resistance, a trait that is correlated with poor patient outcomes. By targeting the metabolic pathways that import, catabolize, and synthesize essential cellular components, drug resistant cancer cells can often be resensitized to anti-cancer treatments. The specificity and efficacy of agents directed at the unique aspects of cancer metabolism is expected to be high; and may, when in utilized in combination with more traditional therapeutics, present a pathway to surmount resistance within tumors that no longer respond to current forms of treatment.