Department of Urology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Guangdong Key Laboratory of Urology, Department of Urology, Minimally Invasive Surgery Center, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
J Cell Physiol. 2021 Mar;236(3):1616-1627. doi: 10.1002/jcp.29969. Epub 2020 Aug 11.
Renal cell carcinoma (RCC) is one of the most common tumours of the urinary system, and is insidious and not susceptible to chemoradiotherapy. As the most common subtype of RCC (70-80% of cases), clear cell renal cell carcinoma (ccRCC) is characterized by the loss of von Hippel-Lindau and the accumulation of robust lipid and glycogen. For advanced RCC, molecular-targeted drugs, tyrosine kinase inhibitors (TKIs) and the immune checkpoint inhibitors (ICIs) have been increasingly recommended and investigated. Due to the existence of a highly dynamic, adaptive and heterogeneous tumour microenvironment (TME), and due to the glucose and lipid metabolism in RCC, this cancer may be accompanied by various types of resistance to TKIs and ICIs. With the increased production of lactate, nitric oxide, and other new by-products of metabolism, novel findings of the TME and key metabolic enzymes drived by HIF and other factors have been increasingly clarified in RCC carcinogenesis and therapy. However, there are few summaries of the TME and tumour metabolism for RCC progression and therapy. Here, we summarize and discuss the relationship of the important implicated characteristics of the TME as well as metabolic molecules and RCC carcinogenesis to provide prospects for future treatment strategies to overcome TME-related resistance in RCC.
肾细胞癌（RCC）是泌尿系统最常见的肿瘤之一，其隐匿且不易接受放化疗。透明细胞肾细胞癌（ccRCC）作为 RCC 最常见的亚型（占 70-80%的病例），其特征是von Hippel-Lindau 的缺失和丰富的脂质和糖原的积累。对于晚期 RCC，分子靶向药物、酪氨酸激酶抑制剂（TKIs）和免疫检查点抑制剂（ICIs）已被越来越多地推荐和研究。由于存在高度动态、适应性和异质性的肿瘤微环境（TME），以及 RCC 中的葡萄糖和脂质代谢，这种癌症可能伴随着各种类型的对 TKIs 和 ICI 的耐药性。由于乳酸、一氧化氮和其他代谢新产物的大量产生，HIF 等因素驱动的 TME 和关键代谢酶的新发现，在 RCC 的发生和治疗中得到了越来越多的阐明。然而，对于 TME 和肿瘤代谢与 RCC 进展和治疗的关系，很少有综述进行总结和讨论。在这里，我们总结和讨论了 TME 以及代谢分子与 RCC 发生的重要相关特征之间的关系，为克服 RCC 中与 TME 相关的耐药性提供了未来治疗策略的前景。
