Inhibiting Autophagy in Renal Cell Cancer and the Associated Tumor Endothelium.
Inhibiting Autophagy in Renal Cell Cancer and the Associated Tumor Endothelium.
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DOI：
10.1097/ppo.0000000000000374
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发表时间：
2019
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肾癌的透明细胞亚型包括大多数肾细胞癌病例，并且与von Hippel-Lindau基因功能或表达的丧失相关。其他等位基因的后续丢失或突变影响涉及营养和缺氧传感的细胞应激反应。自噬是一个重要的调节过程，促进处理不必要的或降解的细胞成分，与几乎所有的细胞过程紧密相连。细胞内受损或不再需要的细胞器和蛋白质在与溶酶体融合后在自噬体中被隔离和消化，或者通过囊泡胞吐作用释放。肿瘤的发展往往会破坏这一过程和细胞凋亡之间的平衡调节，从而延长细胞存活和增加复制。使用羟氯喹与其他抗癌药物（包括雷帕霉素类似物和高剂量白细胞介素2）联合使用的自噬抑制剂的已完成试验现已报道。自噬的复杂性质和透明细胞肾细胞癌的独特生物学需要进一步了解，以更好地开发下一代相关抗癌药物。
The clear cell subtype of kidney cancer encompasses most renal cell carcinoma cases and is associated with the loss of von Hippel-Lindau gene function or expression. Subsequent loss or mutation of the other allele influences cellular stress responses involving nutrient and hypoxia sensing. Autophagy is an important regulatory process promoting the disposal of unnecessary or degraded cellular components, tightly linked to almost all cellular processes. Organelles and proteins that become damaged or that are no longer needed in the cell are sequestered and digested in autophagosomes upon fusing with lysosomes, or alternatively, released via vesicular exocytosis. Tumor development tends to disrupt the regulation of the balance between this process and apoptosis, permitting prolonged cell survival and increased replication. Completed trials of autophagic inhibitors using hydroxychloroquine in combination with other anticancer agents including rapalogues and high dose Interleukin 2 have now been reported. The complex nature of autophagy and the unique biology of clear cell renal cell carcinoma warrant further understanding to better develop the next generation of relevant anticancer agents.