title: mTOR Inhibition and Clinical Transplantation: Pancreas and Islet.
abstract: This brief overview discusses the beneficial and deleterious effects of mammalian target of rapamycin (mTOR) inhibitors on β cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from greater than 80% to less than 50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to less than 10% currently. This decrease is arguably due to less well-tolerated side effects without the advantage of better outcomes. Nonetheless, mTOR inhibitors remain extremely valuable as second-line immunosuppressants in pancreas and islet transplantation.
authors.affiliation: Division of Transplantation, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.affiliation: Division of Transplantation, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Axel
authors.initials: A
authors.lastname: Andres
authors.affiliation: Division of Transplantation, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
authors.affiliation: Division of Transplantation, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Pietro
authors.initials: P
authors.lastname: Majno
authors.affiliation: Department of Abdominal Surgery and Transplantation, University of Liège, Liège, Belgium.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Squifflet
mesh_terms: D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation; D016035:Pancreas Transplantation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus