靶向肾透明细胞癌糖代谢重编程药物的研究进展

Research progress on glucose metabolism reprogramming drugs targeting renal clear cell carcinoma

肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)是肾癌的最常见类型。近年来,靶向和免疫治疗对于转移性ccRCC的治疗取得了重要进展,但总体预后仍然较差。ccRCC的发生发展以其独特的代谢改变为显著特点,表现为有氧糖酵解(aerobic glycolysis)、磷酸戊糖途径(pentose phosphate pathway,PPP)、脂肪酸合成(fatty acid synthesis)、谷氨酰胺(glutamine)和谷胱甘肽(glutathione)代谢的上调,以及三羧酸循环(tricarboxylic acid cycle,TCA cycle)、脂肪酸β氧化(fatty acidβ-oxidation,FAO)和氧化磷酸化(oxidative phosphorylation,OXPHOS)的下调。这些代谢特征的改变被概括为“代谢重编程”。本文仅以ccRCC中糖代谢重编程为重点,综述ccRCC中糖代谢的变化,以及针对该过程的关键酶及转运体的药物开发,探讨针对ccRCC“糖代谢重编程”进行靶向治疗的意义和研究现状,为ccRCC的治疗提供新思路。

Clear cell renal cell carcinoma(ccRCC)is the most common type of kidney cancer.In recent years,targeted and immunotherapy have made important progress in the treatment of metastatic ccRCC,but the overall prognosis remains poor.Clear cell renal cell carcinoma is characterized by unique metabolic alterations,including upregulation of aerobic glycolysis,the pentose phosphate pathway(PPP),fatty acid synthesis,glutamine and glutathione metabolism,and downregulation of the tricarboxylic acid cycle(TCA cycle),fatty acidβ-oxidation(FAO)and oxidative phosphorylation(OXPHOS).These metabolic changes are summarized as“metabolic reprogramming”.This review focuses on the reprogramming of glucose metabolism in ccRCC,summarizing the alterations in glucose metabolism and the development of inhibitors targeting key enzymes and transporters involved in this process,and providing new strategies for the treatment of ccRCC.