Dual Inhibition of PI3-Kinase and mTOR in Renal Cell Carcinoma

Daniel      C. Cho; James      W. Mier

Abstract

Although PI3-kinase mutations are uncommon in renal cell carcinoma (RCC), the PI3-kinase/Akt signaling pathway is active in most RCC. The activation of PI3-kinase would be expected to drive protein and lipid synthesis through its effects on mTORC1 and SREBP1, respectively. PI3-kinase also activates numerous transcription factors (e.g. the FOXO family, c-myc, NF-κB) that regulate cell proliferation and viability. The consequences of blocking PI3-kinase in RCC are just now beginning to be elucidated and are expected to include effects on tumor cell proliferation, metabolism, and angiogenesis. Several PI3-kinase inhibitors currently undergoing clinical testing are active site inhibitors of mTOR as well and it is likely that these agents will prove particularly useful in the treatment of RCC.

Keywords: Everolimus, mTOR, renal cell carcinoma, PI3-kinase, temsirolimus, translation.

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