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阻止抵抗引擎:针对癌症代谢以克服治疗抵抗。

Stalling the engine of resistance: targeting cancer metabolism to overcome therapeutic resistance.

机构信息

Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama 36604, USA.

出版信息

Cancer Res. 2013 May 1;73(9):2709-17. doi: 10.1158/0008-5472.CAN-12-3009. Epub 2013 Apr 22.

Abstract

Cancer cells are markedly different from normal cells with regards to how their metabolic pathways are used 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 anticancer treatments. The specificity and efficacy of agents directed at the unique aspects of cancer metabolism are expected to be high; and may, when in used in combination with more traditional therapeutics, present a pathway to surmount resistance within tumors that no longer respond to current forms of treatment.

摘要

癌细胞在代谢途径的利用上与正常细胞有显著差异,这些代谢途径用于为细胞生长和存活提供燃料。两种基本代谢物——葡萄糖和谷氨酰胺——通过增加摄取和改变代谢利用来体现这些差异。这些分子可以分解代谢以制造许多用于活跃细胞生长和增殖的构建块。维持这种生长所需的代谢途径的改变与治疗抵抗有关,这种特性与患者预后不良相关。通过靶向导入、分解代谢和合成必需细胞成分的代谢途径,耐药癌细胞通常可以重新对癌症治疗敏感。针对癌症代谢独特方面的药物的特异性和疗效预计会很高;并且当与更传统的疗法联合使用时,可能为克服对当前治疗形式不再响应的肿瘤中的耐药性提供一种途径。

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