Sustained proliferative potential of cancer cells creates heightened energetic and biosynthetic demands. The resulting overt dependence of cancer cells on unperturbed nutrient supply has prompted a widespread interest in amino acid restriction strategies as potential cancer therapeutics. However, owing to rapid signaling and metabolic reprogramming in cancer cells, the prospects for success of amino acid restriction approaches remain unclear. We thus recognize that the identification of co-vulnerabilities of amino acid-restricted cancers may inform actionable targets for effective combined interventions. In this perspective, we outline the current state of key cellular mechanisms underlying adaptation to amino acid restriction and discuss the role of signal transduction pathways governing cancer cell resistance to amino acid restriction, with potential ramifications for the design of future therapeutic efforts.

癌细胞的持续增殖潜力创造了更高的能量和生物合成需求。由此产生的癌细胞对不受干扰的营养供应的明显依赖引起了人们对氨基酸限制策略作为潜在癌症治疗剂的广泛兴趣。然而，由于癌细胞中的快速信号传导和代谢重编程，氨基酸限制方法的成功前景仍不清楚。因此，我们认识到氨基酸限制性癌症的共同脆弱性的识别可能为有效联合干预的可操作目标提供信息。从这个角度来看，我们概述了适应氨基酸限制的关键细胞机制的当前状态，并讨论了控制癌细胞对氨基酸限制抗性的信号转导途径的作用，