Rapamycine and mTOR inhibitors: from bench to bedside

Rapamycin is a macrocyclic lactone with antifungal and antibiotic properties isolated from Streptonqces hygroscopicus during the 70's. Studies of rapamycin properties in yeast led to the discovery of TOR (Target Of Raparnycin) and its marnmalian analogue, mTOR. mTOR is a central regulator of cell growth and proliferation in response to environmental stimuli such as growth factors or nutrients. There are two proteins that have been shown to be regulated by mTOR in response to a broad range of mitogenic stimuli. The translation regulation induced by mTOR is mediated by the p70 S6 kinase activation and the 4E-BPI inhibition. Both proteins participate in the regulation of translation process and growth in cells stimulated by either mitogens or hormones. Antiproliferative effects of rapamycin and analogues have been demonstrated on numerous cell types, explaining the development of these drugs in clinical practice: as immunosuppressive drugs in solid or-an transplantation, in oncology for the treatment of various types of cancer, and for the prevention of restenosis after coronary angioplasty. Raparnycin is a potent immunosuppressive drug used in solid organ transplantation for the prevention of acute rejection. In oncology these antiproliferative effects are evaluated in several types of cancers. Rapamycin is now widely used for coating stents to reduce post-stenting restenosis phenomenon after coronary angioplasty. Finally, rapamycin is now evaluated in various diseases characterized by proliferative disorders.