Faes Seraina, Demartines Nicolas, Dormond Olivier
Department of Visceral Surgery, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
Front Cell Dev Biol. 2021 Mar 15;9:636037. doi: 10.3389/fcell.2021.636037. eCollection 2021.
Several elements highlight the importance of the mechanistic target of rapamycin (mTOR) in the biology of renal cell carcinoma (RCC). mTOR signaling pathway is indeed frequently activated in RCC, inducing cancer cell proliferation and survival. In addition, mTOR promotes tumor angiogenesis and regulates the expression of hypoxia-inducible factors that play an important role in a subset of RCC. Despite mTOR protumorigenic effects, mTOR inhibitors have failed to provide long-lasting anticancer benefits in RCC patients, highlighting the need to readdress their role in the treatment of RCC. This review aims to present the rationale and limitations of targeting mTOR in RCC. Future roles of mTOR inhibitors in the treatment of RCC are also discussed, in particular in the context of immunotherapies.
几个因素凸显了雷帕霉素的作用机制靶点(mTOR)在肾细胞癌(RCC)生物学中的重要性。mTOR信号通路在RCC中确实经常被激活,从而诱导癌细胞增殖和存活。此外,mTOR促进肿瘤血管生成并调节缺氧诱导因子的表达,这些因子在一部分RCC中发挥重要作用。尽管mTOR具有促肿瘤发生的作用,但mTOR抑制剂未能在RCC患者中提供持久的抗癌益处,这凸显了重新审视其在RCC治疗中作用的必要性。本综述旨在阐述在RCC中靶向mTOR的理论依据和局限性。还讨论了mTOR抑制剂在RCC治疗中的未来作用,特别是在免疫治疗背景下的作用。