Document Detail

Targeting the dysregulated mammalian target of rapamycin pathway in organ transplantation: killing 2 birds with 1 stone.
MedLine Citation:
PMID:  21419611     Owner:  NLM     Status:  Publisher    
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 into the 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.
Michael Haidinger; Johannes Werzowa; Thomas Weichhart; Marcus D Säemann
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-16
Journal Detail:
Title:  Transplantation reviews (Orlando, Fla.)     Volume:  -     ISSN:  1557-9816     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804364     Medline TA:  Transplant Rev (Orlando)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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