Chapter 18 - The Role of mTOR Inhibitors in Solid Organ Transplantation

Abstract

Successful organ transplantation requires immunosuppression, however current immunosuppressants have significant side effects, particularly nephrotoxicity. Mammalian target of rapamycin (mTOR) inhibitors are a class of drugs that interfere with the multifaceted mTOR pathway, limiting T-cell proliferation and the alloimmune response. There are two mTOR inhibitors that are approved for organ transplantation: sirolimus and everolimus, and these drugs are used in kidney, liver, and heart transplantation. The development and approval of these medications for transplantation have been controversial and complicated, however these medications also offer many exciting advantages for transplantation. The mTOR pathway is responsible for maintaining cellular homeostasis and it controls numerous cellular processes, thus inhibition of the mTOR pathway by mTOR inhibitors has numerous beneficial effects, including antineoplastic, antiviral, and antiproliferative activity. However, inhibiting the mTOR pathway also leads to numerous diverse adverse side effects. Managing the many side effects is the key to being able to take advantage of the potential benefits.