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Review
. 2021 Mar 15:9:636037.
doi: 10.3389/fcell.2021.636037. eCollection 2021.

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

Seraina Faes  1 , Nicolas Demartines  1 , Olivier Dormond  1
Affiliations
Review

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

Seraina Faes et al. Front Cell Dev Biol. .

Abstract

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.

Keywords: HIF-α; angiogenesis; mTOR; rapalogs; renal cell carcinoma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Rationale to target mechanistic target of rapamycin (mTOR) in renal cell carcinoma (RCC). Components of mTOR signaling pathway are frequently mutated in RCC resulting in mTORC1 overactivation. In turn, mTORC1 promotes tumor cell growth and VEGF production either directly or by upregulating expression levels of hypoxia-inducible factor (HIF)-α factors. In addition mTORC1 promotes endothelial cell functions that are relevant to tumor angiogenesis including endothelial cell proliferation, survival, and migration.
See this image and copyright information in PMC

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