PMID- 23226698
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121212
LR  - 20211021
IS  - 1178-6930 (Electronic)
IS  - 1178-6930 (Linking)
VI  - 5
DP  - 2012
TI  - Prognostic significance of AKT/mTOR signaling in advanced neuroendocrine tumors 
      treated with somatostatin analogs.
PG  - 409-16
LID - 10.2147/OTT.S36330 [doi]
AB  - INTRODUCTION: Somatostatin analogs (SSAs) are used as part of standard treatment 
      for advanced neuroendocrine tumors (NETs). The mechanisms behind the 
      antiproliferative action of SSAs remain largely unknown, but a connection with 
      the mammalian target of rapamycin (mTOR) signaling pathway has been suggested. 
      Our purpose was to evaluate the activation status of the AKT/mTOR pathway in 
      advanced metastatic NETs and identify biomarkers of response to SSA therapy. 
      PATIENTS AND METHODS: Expression of phosphatase and tensin homolog (PTEN), 
      phosphorylated (p)-AKT(Ser473), and p-S6(Ser240/244) was evaluated using 
      immunohistochemistry in archival paraffin samples from 23 patients. Expression 
      levels were correlated with clinicopathological parameters and progression-free 
      survival under treatment with SSAs. RESULTS: A positive association between p-AKT 
      and p-S6 expression was identified (P = 0.01) and higher expression of both 
      markers was observed in pancreatic NETs. AKT/mTOR activation was observed without 
      the loss of PTEN expression. Tumors showing AKT/mTOR signaling activation 
      progressed faster when treated with SSAs: higher expression of p-AKT or p-S6 
      predicted a median progression-free survival of 1 month vs 26.5 months for lower 
      expression (P = 0.02). CONCLUSION: Constitutive activation of the AKT/mTOR 
      pathway was associated with shorter time-to-progression in patients undergoing 
      treatment with SSAs. Larger case series are needed to validate whether 
      p-AKT(Ser473) and p-S6(Ser240/244) can be used as prognostic markers of response 
      to therapy with SSAs.
FAU - Fernandes, Isabel
AU  - Fernandes I
AD  - Department of Medical Oncology, Hospital Santa Maria, CHLN, Lisboa, Portugal; ; 
      Clinical and Translational Oncology Research Unit, Instituto de Medicina 
      Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal;
FAU - Pacheco, Teresa R
AU  - Pacheco TR
FAU - Costa, Adilia
AU  - Costa A
FAU - Santos, Ana C
AU  - Santos AC
FAU - Fernandes, Ana R
AU  - Fernandes AR
FAU - Santos, Mara
AU  - Santos M
FAU - Oliveira, Antonio G
AU  - Oliveira AG
FAU - Casimiro, Sandra
AU  - Casimiro S
FAU - Quintela, Antonio
AU  - Quintela A
FAU - Fernandes, Afonso
AU  - Fernandes A
FAU - Ramos, Madalena
AU  - Ramos M
FAU - Costa, Luis
AU  - Costa L
LA  - eng
PT  - Journal Article
DEP - 20121128
PL  - New Zealand
TA  - Onco Targets Ther
JT  - OncoTargets and therapy
JID - 101514322
PMC - PMC3514972
OTO - NOTNLM
OT  - mTOR pathway
OT  - neuroendocrine tumor
OT  - somatostatin analogs
EDAT- 2012/12/12 06:00
MHDA- 2012/12/12 06:01
PMCR- 2012/11/28
CRDT- 2012/12/11 06:00
PHST- 2012/11/27 00:00 [received]
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2012/12/12 06:01 [medline]
PHST- 2012/11/28 00:00 [pmc-release]
AID - ott-5-409 [pii]
AID - 10.2147/OTT.S36330 [doi]
PST - ppublish
SO  - Onco Targets Ther. 2012;5:409-16. doi: 10.2147/OTT.S36330. Epub 2012 Nov 28.