Overcoming anticancer drug resistance is a major challenge in cancer therapy, requiring innovative strategies that consider the extensive tumor heterogeneity and adaptability. We provide recent evidence highlighting the key role of amino acid (AA) metabolic reprogramming in cancer cells and the supportive microenvironment in driving resistance to anticancer therapies. AAs sustain the acquisition of anticancer resistance by providing essential building blocks for biosynthetic pathways and for maintaining a balanced redox status, and modulating the epigenetic profile of both malignant and non-malignant cells. In addition, AAs support the reduced intrinsic susceptibility of cancer stem cells to antineoplastic therapies. These findings shed new light on the possibility of targeting nonresponding tumors by modulating AA availability through pharmacological or dietary interventions.

克服抗癌药物耐药性是癌症治疗的一大挑战，需要考虑广泛的肿瘤异质性和适应性的创新策略。我们提供了最近的证据，强调了氨基酸 (AA) 代谢重编程在癌细胞中的关键作用以及支持性微环境在驱动抗癌疗法耐药性方面的关键作用。AA 通过为生物合成途径和维持平衡的氧化还原状态提供必要的构建模块，并调节恶性和非恶性细胞的表观遗传谱来维持抗癌抗性的获得。此外，AA 支持降低癌症干细胞对抗肿瘤治疗的内在敏感性。