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.
Highlights
Renal cell carcinoma (RCC), which originates from the kidney epithelium, is the most frequent form of kidney cancer (Hsieh et al, 2017b; Nabi et al, 2018; Kotecha et al, 2019)
Curative surgery is possible in patients with localized RCC (Ljungberg et al, 2015)
It is important to gain further knowledge regarding the biology of RCC in order to design successful therapies
Summary
Renal cell carcinoma (RCC), which originates from the kidney epithelium, is the most frequent form of kidney cancer (Hsieh et al, 2017b; Nabi et al, 2018; Kotecha et al, 2019). Curative surgery is possible in patients with localized RCC (Ljungberg et al, 2015). Many patients present in advanced, metastatic stages at diagnosis, and progression of a localized to an advanced stage is frequent despite surgery. Since advanced RCC is associated with high mortality, a strong need exists to develop appropriate systemic treatments. In this context, major progress has been achieved recently, and today, several therapeutic options exist, including immunotherapy and targeted therapies against vascular endothelial growth factor (VEGF) or mechanistic target of rapamycin (mTOR) signaling pathway (Hsieh et al, 2017b; Kotecha et al, 2019). It is important to gain further knowledge regarding the biology of RCC in order to design successful therapies
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