[mTOR inhibitors: pleiotropic antiproliferative drugs].
Studies of rapamycin properties in yeast led to the discovery of TOR (target of rapamycin) and its mammalian analogue, mTOR. mTOR is a central regulator of cell growth and proliferation in response to environmental stimuli such as growth factors and nutrients. mTOR regulates several pathways, particularly translation process by controlling the activity of two proteins in response to a broad range of mitogenic stimuli, S6K1 and 4E-BP1. Inhibition of cell growth by rapamycine and analogues have been demonstrated in numerous cell types, explaining the broad development of these drugs in clinical practice. Rapamycine is a potent immunosuppressive drug used in solid organ transplantation for the prevention of allograft rejection. In oncology, mTOR inhibitors are currently evaluated in several types of cancers. They are now widely used for coating stents to reduce post-stenting restenosis after coronary angioplasty. Finally, rapamycine is now evaluated in various diseases characterized by cell growth disorders such as phacomatosis and autosomal dominant polycystic kidney disease.
Pallet
Nicolas
N
Service de Transplantation Rénale, Hôpital Necker, AP-HP, Université Paris V-René Descartes, 149, Rue de Sèvres, 75015 Paris, France. nicolas.pallet@univ-paris5.fr
Beaune
Philippe
P
Thervet
Eric
E
Legendre
Christophe
C
Anglicheau
Dany
D
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D006130:Growth Disorders / Q000188:drug therapy; D006706:Homeostasis; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008322:Mammals; D007690:Polycystic Kidney Diseases / Q000188:drug therapy / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000494:pharmacology / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases