PMID- 26071984
OWN - NLM
STAT- MEDLINE
DCOM- 20160422
LR  - 20220310
IS  - 1557-9816 (Electronic)
IS  - 0955-470X (Linking)
VI  - 29
IP  - 3
DP  - 2015 Jul
TI  - mTOR inhibitor therapy: Does it prevent HCC recurrence after liver 
      transplantation?
PG  - 168-74
LID - S0955-470X(15)00007-5 [pii]
LID - 10.1016/j.trre.2015.02.003 [doi]
AB  - Prevention of hepatocellular carcinoma (HCC) recurrence after liver 
      transplantation is a clinical priority. The importance of the mammalian target of 
      rapamycin (mTOR) pathway in cell growth and survival makes it a logical target 
      for antitumor strategies, as borne out by clinical data in various types of 
      malignancy. A number of studies have indicated that the mTOR inhibitors 
      everolimus and sirolimus suppress cell proliferation and tumor growth in animal 
      models of HCC. Coadministration of an mTOR inhibitor could permit lower dosing of 
      chemotherapeutic agents in HCC management, and trials in non-transplant HCC 
      population are exploring combined used with various agents including sorafenib, 
      the vascular endothelial growth factor inhibitor bevacizumab and conventional 
      agents. In terms of a preventive effect after liver transplantation for HCC, data 
      from retrospective studies and non-randomized prospective analyses in which 
      patients received an mTOR inhibitor with concomitant calcineurin inhibitor 
      therapy have indicated that HCC recurrence rates and overall survival may be 
      improved compared to a standard calcineurin inhibitor regimen. Meta-analyses have 
      supported these findings, but controlled trials are required before any firm 
      conclusions can be drawn. In two of the three randomized trials which have 
      assessed de novo mTOR inhibitor therapy after liver transplantation, there was a 
      numerically lower rate of HCC recurrence by one year post-transplant in patients 
      given an mTOR inhibitor versus the control arm, but absolute numbers were low. 
      Overall, based on the available data from retrospective studies, meta-analyses, 
      and post-hoc assessments of randomized trials, it appears advisable to consider 
      mTOR inhibition-based immunosuppression after transplantation for HCC, 
      particularly in patients who exceed the Milan criteria. Prospective data are 
      awaited.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Duvoux, Christophe
AU  - Duvoux C
AD  - Department of Hepatology and Liver Transplant Unit Henri Mondor Hospital, Paris 
      Est University (UPEC), 51 Avenue du Marechal de Lattre de Tassigny, 94010 
      Creteil, France; Division of Abdominal and Transplantation Surgery, Department of 
      Surgery, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva, 
      Switzerland. Electronic address: christophe.duvoux@hmn.aphp.fr.
FAU - Toso, Christian
AU  - Toso C
AD  - Department of Hepatology and Liver Transplant Unit Henri Mondor Hospital, Paris 
      Est University (UPEC), 51 Avenue du Marechal de Lattre de Tassigny, 94010 
      Creteil, France; Division of Abdominal and Transplantation Surgery, Department of 
      Surgery, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva, 
      Switzerland.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150225
PL  - United States
TA  - Transplant Rev (Orlando)
JT  - Transplantation reviews (Orlando, Fla.)
JID - 8804364
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Carcinoma, Hepatocellular/pathology/*surgery
MH  - Everolimus/therapeutic use
MH  - Female
MH  - Humans
MH  - Liver Neoplasms/pathology/*surgery
MH  - Liver Transplantation/*adverse effects/methods
MH  - Male
MH  - Neoplasm Recurrence, Local/drug therapy/*prevention & control
MH  - Prognosis
MH  - Randomized Controlled Trials as Topic
MH  - Risk Assessment
MH  - Sirolimus/*therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Treatment Outcome
EDAT- 2015/06/15 06:00
MHDA- 2016/04/23 06:00
CRDT- 2015/06/15 06:00
PHST- 2014/10/29 00:00 [received]
PHST- 2015/02/12 00:00 [revised]
PHST- 2015/02/17 00:00 [accepted]
PHST- 2015/06/15 06:00 [entrez]
PHST- 2015/06/15 06:00 [pubmed]
PHST- 2016/04/23 06:00 [medline]
AID - S0955-470X(15)00007-5 [pii]
AID - 10.1016/j.trre.2015.02.003 [doi]
PST - ppublish
SO  - Transplant Rev (Orlando). 2015 Jul;29(3):168-74. doi: 10.1016/j.trre.2015.02.003. 
      Epub 2015 Feb 25.