Mechanistic target of rapamycin inhibitors in solid organ transplantation:  from benchside to clinical use.
OBJECTIVE
Here, we review recent advances and new insights in mechanistic target of rapamycin (mTOR) biology (signalling pathway, kidney biology and immune system), and recent clinical data on mTOR inhibitors related to solid organ transplantation.


RESULTS
The mTOR pathway is a major integrator of signals governing protein and lipid biosynthesis and growth factor-driven cell cycle progression. Recent findings have emphasized a critical role of mTOR in cellular homeostasis with a crucial role in podocyte function. Beyond CD8(+) and regulatory T-cell control, mTOR protein is involved in critical biological functions of T helper cells or dendritic cells. New specific inhibitors of mTORC1/C2 are available and shed new light on mTOR functions. Finally, clinical trials have better defined the use of mTOR inhibitors and emphasized their role in cancer prevention.


CONCLUSIONS
The mTOR pathway is considered as a key integrator of multiple inputs that drives numerous biological processes in cell biology. mTOR inhibitors are potent immunosuppressive drugs for solid organ transplantation. Newly designed specific inhibitors of mTOR complex 1 and 2 offer promising therapeutic effects and a better understanding of the pathway. Many conditions may benefit from mTOR inhibition for a short period, but tolerance of treatment in a chronic setting remains a major concern.
Institut de Transplantation Urologie, Néphrologie and Institut National de la Santé Et de la Recherche Médicale UMR1064, Nantes University Hospital, Nantes, France.
Maxime
M
Touzot
Jean Paul
JP
Soulillou
Jacques
J
Dantal
D065095:Calcineurin Inhibitors; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016377:Organ Transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases