Mechanistic Target of Rapamycin Inhibitors in Renal Cell Carcinoma: Potential, Limitations, and Perspectives

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.

Automated summary

The importance of the mechanistic target of rapamycin (mTOR) in renal cell carcinoma (RCC) biology is highlighted by its frequent activation in RCC, promoting cancer cell proliferation and survival. Despite its protumorigenic effects, mTOR inhibitors have not provided long-lasting anticancer benefits in RCC patients, calling for a reevaluation of their role in treatment. This review presents the rationale and limitations of targeting mTOR in RCC, as well as discussing the future roles of mTOR inhibitors in RCC treatment, especially in the context of immunotherapies.