Dept of Oncology-Pathology, CCK R8:03, Karolinska Institute, S-171 76 Stockholm, Sweden.
Curr Pharm Biotechnol. 2013;14(3):313-30. doi: 10.2174/1389201011314030007.
Oncogene-driven proliferative signaling in tumor cells requires comprehensive upregulation of cellular energy metabolism and macromolecule syntheses. These alterations are now known to include not only upregulated glycolysis, but also increased fatty acid metabolism, glutaminolysis, deregulated mitochondrial function and more. Many prospective targets for tumor-specific pharmacological modulation of metabolism have therefore been identified. While the prospective drugs do not necessarily show very high antitumor activity by themselves, they may by depriving tumor cells of energy and building blocks for repair and proliferation come to be of major clinical use as potentiators of standard chemotherapeutic drugs and/or radiation. To this end, not only inhibitors of specific enzyme functions are being investigated, but also drugs affecting the complex signaling networks that regulate organismal and cellular energy status. This review provides examples of how modulators of energy metabolism (MEMs) targetting different aspects of tumor cell metabolism have been found to potentiate cancer treatment in vitro and in vivo.
癌基因驱动的肿瘤细胞增殖信号需要全面上调细胞能量代谢和大分子合成。现在已知这些改变不仅包括上调的糖酵解，还包括增加脂肪酸代谢、谷氨酰胺分解、线粒体功能失调等。因此，已经确定了许多针对肿瘤代谢特异性药理调节的潜在靶点。虽然这些潜在药物本身不一定具有非常高的抗肿瘤活性，但它们通过剥夺肿瘤细胞的能量和修复及增殖所需的构建块，可能成为标准化疗药物和/或放疗的增效剂而具有重要的临床应用价值。为此，不仅研究了特定酶功能的抑制剂，还研究了影响调节机体和细胞能量状态的复杂信号网络的药物。本综述提供了一些例子，说明靶向肿瘤细胞代谢不同方面的能量代谢调节剂 (MEMs) 如何在体外和体内增强癌症治疗。
