Alterations in cellular sugar, amino acid and nucleic acid, and lipid metabolism, as well as in mitochondrial function, are a hallmark of renal cell carcinoma (RCC). The activation of oncogenes such as hypoxia-inducible factor and loss of the von Hippel-Lindau function and other tumor suppressors frequently occur early on during tumorigenesis and are the drivers for these changes, collectively known as “metabolic reprogramming,” which promotes cellular growth, proliferation, and stress resilience. However, tumor cells can become addicted to reprogrammed metabolism. Here, we review the current knowledge of metabolic addictions in clear cell RCC, the most common form of RCC, and to what extent this has created therapeutic opportunities to interfere with such altered metabolic pathways to selectively target tumor cells. We highlight preclinical and emerging clinical data on novel therapeutics targeting metabolic traits in clear cell RCC to provide a comprehensive overview on current strategies to exploit metabolic reprogramming clinically.

细胞糖、氨基酸和核酸、脂质代谢以及线粒体功能的改变是肾细胞癌(RCC)的标志。癌基因的激活，如缺氧诱导因子和 von Hippel-Lindau 功能的丧失和其他肿瘤抑制因子，经常发生在肿瘤发生的早期，并且是这些变化的驱动因素，统称为“代谢重编程”，可促进细胞生长，增殖和抗压能力。然而，肿瘤细胞会沉迷于重新编程的代谢. 在这里，我们回顾了目前对透明细胞 RCC（最常见的 RCC 形式）中代谢成瘾的了解，以及这在多大程度上创造了干扰这种改变的代谢途径以选择性靶向肿瘤细胞的治疗机会。我们重点介绍了针对透明细胞 RCC 代谢特征的新型疗法的临床前和新兴临床数据，以全面概述目前在临床上利用代谢重编程的策略。