Dual inhibition of PI3-kinase and mTOR in renal cell carcinoma.

Abstract

Although PI3-kinase mutations are uncommon in renal cell carcinoma (RCC), the PI3-kinase/Akt signalingpathway is active in most RCC. The activation of PI3-kinase would be expected to drive protein and lipid synthesisthrough 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-kinasein 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 inhibitorsof mTOR as well and it is likely that these agents will prove particularly useful in the treatment of RCC.

• Authors: Daniel C Cho, James W Mier
• Journal: Current cancer drug targets (Curr Cancer Drug Targets) Vol. 13 Issue 2 Pg. 126-42 (Feb 2013) ISSN: 1873-5576 [Electronic] Netherlands
• PMID: 23259857 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Phosphoinositide-3 Kinase Inhibitors
• MTOR protein, human
• TOR Serine-Threonine Kinases

Topics

• Carcinoma, Renal Cell (drug therapy, enzymology, metabolism)
• Cell Division
• Clinical Trials as Topic
• Enzyme Activation
• Humans
• Kidney Neoplasms (drug therapy, enzymology, metabolism, pathology)
• Neovascularization, Pathologic
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Signal Transduction
• TOR Serine-Threonine Kinases (antagonists & inhibitors)