Table 2 Components of the PI3K-Akt-mTOR Pathway Deregulated in RCC
From: Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy
Target | Type of Protein | Genetic Aberration | Potential Relevance in RCC |
|---|---|---|---|
IGF-1, IGF-1R [99] | Growth factor, tyrosine kinase receptor | Overexpression | Patients with IGF-1R+ clear cell RCC (ccRCC) have shorter survival than those with IGF-1R-negative ccRCC [100] |
PTEN [91] | Lipid phosphatase | Silencing, allele loss | PTEN expression may be lost early in RCC carcinogenesis [101] PTEN-deficient tumor cells have increased sensitivity to mTOR inhibition [102] |
TSC1/TSC2 [12] | TSC complex protein | Hereditary loss | Hereditary loss leads to an increased incidence of several tumor types, including kidney tumors [12]. The TSC tumor suppressors are key components in the upstream regulation of mTOR [103]. |
VHL [98] | Ubiquitin ligase | Loss of heterozygosity, mutation, silencing | Up to 75% of clear cell RCCs have lost the function of the von Hippel-Lindau (VHL) gene [11], resulting in accumulation of HIF-1α, a protein that controls the expression of genes involved in angiogenesis. |