Kidney cancer is the seventh leading cause of cancer in the world, and its incidence is on the rise. Renal cell carcinoma (RCC) is the most common form and is a heterogeneous disease comprising three major subtypes that vary in their histology, clinical course and driver mutations. These subtypes include clear cell RCC, papillary RCC and chromophobe RCC. Molecular analyses of hereditary and sporadic forms of RCC have revealed that this complex and deadly disease is characterized by metabolic pathway alterations in cancer cells that lead to deregulated oxygen and nutrient sensing, as well as impaired tricarboxylic acid cycle activity. These metabolic changes facilitate tumour growth and survival. Specifically, studies of the metabolic features of RCC have led to the discovery of oncometabolites — fumarate and succinate — that can promote tumorigenesis, moonlighting functions of enzymes, and substrate auxotrophy owing to the disruption of pathways that enable the production of arginine and cholesterol. These metabolic alterations within RCC can be exploited to identify new therapeutic targets and interventions, in combination with novel approaches that minimize the systemic toxicity of metabolic inhibitors and reduce the risk of drug resistance owing to metabolic plasticity.

肾癌是世界第七大癌症原因，其发病率呈上升趋势。肾细胞癌 (RCC) 是最常见的形式，是一种异质性疾病，包含三种主要亚型，其组织学、临床过程和驱动突变各不相同。这些亚型包括透明细胞肾细胞癌、乳头状肾细胞癌和嫌色细胞肾细胞癌。对遗传性和散发性肾细胞癌的分子分析表明，这种复杂而致命的疾病的特点是癌细胞代谢途径的改变，导致氧和营养感应失调，以及三羧酸循环活性受损。这些代谢变化促进肿瘤生长和存活。具体来说，对肾细胞癌代谢特征的研究发现了致癌代谢物——富马酸和琥珀酸——它们可以促进肿瘤发生、酶的兼职功能以及由于精氨酸和胆固醇产生途径的破坏而导致底物营养缺陷。RCC 内的这些代谢改变可用于确定新的治疗靶点和干预措施，并结合最大限度地减少代谢抑制剂的全身毒性并降低由于代谢可塑性而产生耐药性的风险的新方法。