Translational control and cancer therapy.
Our recent findings on Rheb and eIF4E address key questions of translational control in cancer and have implications for tumor therapy.(1) Briefly, we find that Rheb a proximal activator of mTORC1 and protein translation can cooperate with c-Myc in tumorigenesis in vivo in a manner resembling Akt or the oncogenic eIF4E translation initiation factor. Rheb is highly expressed in some human lymphomas as well as other cancers and likely contributes to malignancies in different tissues.(2) The cancer-relevant activities emanating from increased Rheb depend on activation of mTORC1 and are sensitive to rapamycin. Moreover, farnesyltransferase inhibitors (FTIs) can directly block Rheb activity and this is responsible for the therapeutic effect of these drugs in certain tumors. We will discuss here how translational control mechanisms contribute to oncogenesis and speculate on the potential and limitations of targeting these co-operating oncogenic events for therapy.
Mavrakis
Konstantinos J
KJ
Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Wendel
Hans-Guido
HG
D000818:Animals; D002645:Chickens; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy*; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
D039561:Eukaryotic Initiation Factor-4E; D016271:Proto-Oncogene Proteins c-myc; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins