Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon 21983, Korea.
Department of Integrated OMICS for Biomedical Science, Yonsei University, Seoul 03722, Korea.
Cells. 2022 Jan 2;11(1):140. doi: 10.3390/cells11010140.
Despite the numerous investigations on resistance mechanisms, drug resistance in cancer therapies still limits favorable outcomes in cancer patients. The complexities of the inherent characteristics of tumors, such as tumor heterogeneity and the complicated interaction within the tumor microenvironment, still hinder efforts to overcome drug resistance in cancer cells, requiring innovative approaches. In this review, we describe recent studies offering evidence for the essential roles of amino acid metabolism in driving drug resistance in cancer cells. Amino acids support cancer cells in counteracting therapies by maintaining redox homeostasis, sustaining biosynthetic processes, regulating epigenetic modification, and providing metabolic intermediates for energy generation. In addition, amino acid metabolism impacts anticancer immune responses, creating an immunosuppressive or immunoeffective microenvironment. A comprehensive understanding of amino acid metabolism as it relates to therapeutic resistance mechanisms will improve anticancer therapeutic strategies.
尽管已经对耐药机制进行了大量研究,但癌症治疗中的耐药性仍然限制了癌症患者的良好预后。肿瘤固有特征的复杂性,如肿瘤异质性和肿瘤微环境内的复杂相互作用,仍然阻碍了克服癌细胞耐药性的努力,需要创新的方法。在这篇综述中,我们描述了最近的研究证据,这些证据表明氨基酸代谢在驱动癌细胞耐药性方面起着重要作用。氨基酸通过维持氧化还原平衡、维持生物合成过程、调节表观遗传修饰以及为能量生成提供代谢中间产物,支持癌细胞对抗治疗。此外,氨基酸代谢影响抗肿瘤免疫反应,形成免疫抑制或免疫有效微环境。全面了解氨基酸代谢与治疗耐药机制的关系将改善抗肿瘤治疗策略。