Fei Cao, Zhen Xu, Shiqiang Zhang, Jun Pang
Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
Cell Death Discov. 2024 Mar 5;10(1):113. doi: 10.1038/s41420-024-01880-0.
Clear cell renal cell carcinoma (ccRCC) is one of the most common renal malignancies of the urinary system. Patient outcomes are relatively poor due to the lack of early diagnostic markers and resistance to existing treatment options. Programmed cell death, also known as apoptosis, is a highly regulated and orchestrated form of cell death that occurs ubiquitously throughout various physiological processes. It plays a crucial role in maintaining homeostasis and the balance of cellular activities. The combination of immune checkpoint inhibitors plus targeted therapies is the first-line therapy to advanced RCC. Immune checkpoint inhibitors(ICIs) targeted CTLA-4 and PD-1 have been demonstrated to prompt tumor cell death by immunogenic cell death. Literatures on the rationale of VEGFR inhibitors and mTOR inhibitors to suppress RCC also implicate autophagic, apoptosis and ferroptosis. Accordingly, investigations of cell death modes have important implications for the improvement of existing treatment modalities and the proposal of new therapies for RCC. At present, the novel modes of cell death in renal cancer include ferroptosis, immunogenic cell death, apoptosis, pyroptosis, necroptosis, parthanatos, netotic cell death, cuproptosis, lysosomal-dependent cell death, autophagy-dependent cell death and mpt-driven necrosis, all of which belong to programmed cell death. In this review, we briefly describe the classification of cell death, and discuss the interactions and development between ccRCC and these novel forms of cell death, with a focus on ferroptosis, immunogenic cell death, and apoptosis, in an effort to present the theoretical underpinnings and research possibilities for the diagnosis and targeted treatment of ccRCC.
透明细胞肾细胞癌（ccRCC）是泌尿系统最常见的肾脏恶性肿瘤之一。由于缺乏早期诊断标志物以及对现有治疗方案存在抗性，患者的预后相对较差。程序性细胞死亡，也称为凋亡，是一种高度受调控且精心编排的细胞死亡形式，在各种生理过程中普遍存在。它在维持体内平衡和细胞活动平衡方面发挥着关键作用。免疫检查点抑制剂联合靶向治疗是晚期肾细胞癌的一线治疗方法。靶向细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和程序性死亡蛋白1（PD-1）的免疫检查点抑制剂已被证明可通过免疫原性细胞死亡促使肿瘤细胞死亡。关于血管内皮生长因子受体（VEGFR）抑制剂和雷帕霉素靶蛋白（mTOR）抑制剂抑制肾细胞癌原理的文献也涉及自噬、凋亡和铁死亡。因此，对细胞死亡模式的研究对于改善现有治疗方式以及提出肾细胞癌的新治疗方法具有重要意义。目前，肾癌中的新型细胞死亡模式包括铁死亡、免疫原性细胞死亡、凋亡、焦亡、坏死性凋亡、副凋亡、NETosis细胞死亡、铜死亡、溶酶体依赖性细胞死亡、自噬依赖性细胞死亡和线粒体通透性转换孔（MPT）驱动的坏死，所有这些都属于程序性细胞死亡。在本综述中，我们简要描述细胞死亡的分类，并讨论ccRCC与这些新型细胞死亡形式之间的相互作用和发展，重点关注铁死亡、免疫原性细胞死亡和凋亡，以期为ccRCC的诊断和靶向治疗提供理论基础和研究方向。
