Official reprint from UpToDate®
www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medline ® Abstract for Reference 90

of 'Renal manifestations of tuberous sclerosis complex'

Targeting the dysregulated mammalian target of rapamycin pathway in organ transplantation: killing 2 birds with 1 stone.
Haidinger M, Werzowa J, Weichhart T, Säemann MD
Transplant Rev (Orlando). 2011 Oct;25(4):145-53. Epub 2011 Mar 17.
Dysregulation and hyperactivation of the mammalian target of rapamycin (mTOR) pathway define the molecular basis of the hamartoma syndromes, including Cowden syndrome, tuberous sclerosis complex (TSC)/lymphangioleiomyomatosis, and Peutz-Jeghers syndrome. Loss of the tumor suppressors phosphatase and tensin homolog (PTEN), TSC1, TSC2, and LKB1 results in uncontrolled growth of usually benign tumors in various organs that, however, frequently lead to organ failure. Therefore, organ transplantation is a common therapeutic option in distinct patients with hamartoma syndromes, especially those with TSC/lymphangioleiomyomatosis. mTOR inhibitors are currently used in allogeneic transplantation as immunosuppressants and for the treatment of a growing number of cancers with dysregulated mTOR/phosphoinositide 3-kinase pathway. This dual targeting provides the unique opportunity for mTOR inhibitors to affect hamartoma syndromes at the molecular level along with potent immunosuppression in transplanted individuals. Here, we review the molecular mechanisms of hamartoma syndromes and discuss the recent clinical progress in transplant patients with hamartomas. Combining the identification of novel molecular targets of the phosphoinositide 3-kinase/mTOR pathway with insights intothe clinical effectiveness of current therapeutic strategies sets the stage for a broader translational potential essential for further progress both in the treatment of cancer and for transplantation.
Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Wien, Austria.