title: 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.affiliation: Division of Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, 375 Longwood Avenue, Boston, MA 02215, USA. dcho@bidmc.harvard.edu
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Cho
authors.forename: James W
authors.initials: JW
authors.lastname: Mier
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D002455:Cell Division; D002986:Clinical Trials as Topic; D004789:Enzyme Activation; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human