mTOR and cancer therapy.
Proteins regulating the mammalian target of rapamycin (mTOR), as well as some of the targets of the mTOR kinase, are overexpressed or mutated in cancer. Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo. Results from clinical trials indicate that the rapalogs may be useful for the treatment of subsets of certain types of cancer. The sporadic responses from the initial clinical trials, based on the hypothesis of general translation inhibition of cancer cells are now beginning to be understood owing to a more complete understanding of the dynamics of mTOR regulation and the function of mTOR in the tumor microenvironment. This review will summarize the preclinical and clinical data and recent discoveries of the function of mTOR in cancer and growth regulation.
Easton
J B
JB
Department of Molecular Pharmacology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Houghton
P J
PJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001343:Autophagy; D015687:Cell Hypoxia; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology*; D020123:Sirolimus / Q000627:therapeutic use; D013234:Stem Cells / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D000903:Antibiotics, Antineoplastic; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human