Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133 Rome, Italy.
Biochemistry Laboratory, Istituto Dermopatico Immacolata (IDI-IRCCS), 00100 Rome, Italy.
Int J Mol Sci. 2022 May 31;23(11):6198. doi: 10.3390/ijms23116198.
The understanding of the pathogenesis of renal cell carcinoma led to the development of targeted therapies, which dramatically changed the overall survival rate. Nonetheless, despite innovative lines of therapy accessible to patients, the prognosis remains severe in most cases. Kidney cancer rarely shows mutations in the genes coding for proteins involved in programmed cell death, including p53. In this paper, we show that the molecular machinery responsible for different forms of cell death, such as apoptosis, ferroptosis, pyroptosis, and necroptosis, which are somehow impaired in kidney cancer to allow cancer cell growth and development, was reactivated by targeted pharmacological intervention. The aim of the present review was to summarize the modality of programmed cell death in the pathogenesis of renal cell carcinoma, showing in vitro and in vivo evidence of their potential role in controlling kidney cancer growth, and highlighting their possible therapeutic value.
对肾细胞癌发病机制的认识导致了靶向治疗的发展，这极大地改变了总体生存率。尽管患者可获得创新的治疗方法，但在大多数情况下预后仍然严重。肾癌细胞很少出现涉及程序性细胞死亡的蛋白质编码基因的突变，包括 p53。在本文中，我们表明，负责不同形式细胞死亡（如细胞凋亡、铁死亡、细胞焦亡和坏死性凋亡）的分子机制在肾癌细胞中受到了某种程度的抑制，从而允许癌细胞生长和发展，但通过靶向药理干预可以重新激活这些机制。本综述的目的是总结程序性细胞死亡在肾细胞癌发病机制中的方式，展示体外和体内证据表明它们在控制肾癌细胞生长方面的潜在作用，并强调它们可能的治疗价值。
