PMID- 22886906
OWN - NLM
STAT- MEDLINE
DCOM- 20130307
LR  - 20211203
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 7
IP  - 3
DP  - 2012 Sep
TI  - Inhibition of mTOR in carcinoid tumors.
PG  - 189-95
LID - 10.1007/s11523-012-0225-x [doi]
AB  - Neuroendocrine neoplasms (NEN) are a heterogeneous group of tumors, whose 
      incidence and prevalence are increasing. The clinical behavior of NEN is 
      variable, ranging from well-differentiated slow growing tumors to highly 
      aggressive poorly differentiated neuroendocrine carcinomas. The term carcinoid is 
      commonly used for the more benign variants of these neoplasms. Most frequently, 
      carcinoids have their origin in the small intestine, followed by in the lung and 
      other sites. Some of these tumors are associated with the carcinoid syndrome. The 
      use of somatostatin analogs has revolutionized the clinical management of 
      patients with carcinoids. However, although symptomatic relief and stabilization 
      of tumor growth for various periods of time are observed in many patients treated 
      with somatostatin analogs, tumor regression is rare. Currently, there is no other 
      powerful antiproliferative agent available for carcinoids. Mammalian target of 
      rapamycin (mTOR), a main protein kinase in the phosphoinositide 
      3-kinase/Akt/p70S6K signaling pathway, is an important intracellular mediator 
      involved in multiple cellular functions including proliferation, differentiation, 
      apoptosis, tumorigenesis, and angiogenesis. Alterations of the normal activity of 
      mTOR and of mTOR-related kinases in this pathway have been found in a diversity 
      of human tumors, including NEN; therefore, mTOR pathway represents an attractive 
      target for new anticancer therapies. While mTOR inhibitors, such as everolimus, 
      are established therapy in pancreatic NEN, results from recent clinical trials 
      indicate that mTOR inhibitors may be also of value in the management of 
      carcinoids. However, further clinical trials will have to confirm efficacy and 
      elucidate, in which subtypes and in which setting, these drugs might be most 
      usefully applied.
FAU - Grozinsky-Glasberg, Simona
AU  - Grozinsky-Glasberg S
AD  - Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew 
      University Hospital, Jerusalem, Israel. simonag@hadassah.org.il
FAU - Pavel, Marianne
AU  - Pavel M
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20120812
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Antineoplastic Agents)
RN  - 51110-01-1 (Somatostatin)
RN  - 624KN6GM2T (temsirolimus)
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
EIN - Target Oncol. 2012 Sep;7(3):197
MH  - Antineoplastic Agents/therapeutic use
MH  - Carcinoid Tumor/*metabolism
MH  - Cell Differentiation
MH  - Everolimus
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Medical Oncology/methods
MH  - Models, Biological
MH  - Neuroendocrine Tumors/*drug therapy
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Signal Transduction
MH  - Sirolimus/analogs & derivatives/therapeutic use
MH  - Somatostatin/analogs & derivatives
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Treatment Outcome
EDAT- 2012/08/14 06:00
MHDA- 2013/03/08 06:00
CRDT- 2012/08/14 06:00
PHST- 2012/07/01 00:00 [received]
PHST- 2012/07/24 00:00 [accepted]
PHST- 2012/08/14 06:00 [entrez]
PHST- 2012/08/14 06:00 [pubmed]
PHST- 2013/03/08 06:00 [medline]
AID - 10.1007/s11523-012-0225-x [doi]
PST - ppublish
SO  - Target Oncol. 2012 Sep;7(3):189-95. doi: 10.1007/s11523-012-0225-x. Epub 2012 Aug 
      12.