PMID- 32022503
OWN - NLM
STAT- MEDLINE
DCOM- 20200716
LR  - 20211204
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Linking)
VI  - 26
IP  - 3
DP  - 2019 Mar 1
TI  - Resistance to targeted treatment of gastroenteropancreatic neuroendocrine tumors.
PG  - R109-R130
LID - ERC-18-0420 [pii]
LID - 10.1530/ERC-18-0420 [doi]
AB  - The mammalian target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase 
      (PI3K)/protein kinase B (Akt)/mTOR signaling. The PI3K/Akt/mTOR pathway has a 
      pivotal role in the oncogenesis of neuroendocrine tumors (NETs). In addition, 
      vascular endothelial growth factor (VEGF) and platelet-derived growth factor 
      (PDGF) drive angiogenesis in NETs and therefore contributes to neuroendocrine 
      tumor development. Hence, mTOR and angiogenesis inhibitors have been developed. 
      Everolimus, a first-generation mTOR inhibitor, has shown significant survival 
      benefit in advanced gastroenteropancreatic NETs. Sunitinib, a pan-tyrosine kinase 
      inhibitor that targets the VEGF receptor, has proven to increase progression-free 
      survival in advanced pancreatic NETs. Nevertheless, primary and acquired 
      resistance to rapalogs and sunitinib has limited the clinical benefit for NET 
      patients. Despite the identification of multiple molecular mechanisms of 
      resistance, no predictive biomarker has made it to the clinic. This review is 
      focused on the mTOR signaling and angiogenesis in NET, the molecular mechanisms 
      of primary and acquired resistance to everolimus and sunitinib and how to 
      overcome this resistance by alternative drug compounds.
CI  - (c) 2019 Society for Endocrinology
FAU - Beyens, Matthias
AU  - Beyens M
AD  - Center of Medical Genetics, University of Antwerp and Antwerp University 
      Hospital, Antwerp, Belgium.
AD  - Center for Oncological Research, University of Antwerp, Antwerp, Belgium.
FAU - Vandamme, Timon
AU  - Vandamme T
AD  - Center of Medical Genetics, University of Antwerp and Antwerp University 
      Hospital, Antwerp, Belgium.
AD  - Center for Oncological Research, University of Antwerp, Antwerp, Belgium.
AD  - Section of Endocrinology, Department of Internal Medicine, Erasmus Medical 
      Center, Rotterdam, the Netherlands.
FAU - Peeters, Marc
AU  - Peeters M
AD  - Center of Medical Genetics, University of Antwerp and Antwerp University 
      Hospital, Antwerp, Belgium.
FAU - Van Camp, Guy
AU  - Van Camp G
AD  - Center of Medical Genetics, University of Antwerp and Antwerp University 
      Hospital, Antwerp, Belgium.
AD  - Center for Oncological Research, University of Antwerp, Antwerp, Belgium.
FAU - Op de Beeck, Ken
AU  - Op de Beeck K
AD  - Center of Medical Genetics, University of Antwerp and Antwerp University 
      Hospital, Antwerp, Belgium.
AD  - Center for Oncological Research, University of Antwerp, Antwerp, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190301
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - Gastro-enteropancreatic neuroendocrine tumor
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Humans
MH  - Intestinal Neoplasms/*drug therapy/pathology
MH  - Neuroendocrine Tumors/*drug therapy/pathology
MH  - Pancreatic Neoplasms/*drug therapy/pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Signal Transduction
MH  - Stomach Neoplasms/*drug therapy/pathology
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - rapalog
OT  - sunitinib
OT  - resistance
OT  - neuroendocrine tumors
OT  - targeted treatment
EDAT- 2020/02/06 06:00
MHDA- 2020/07/17 06:00
CRDT- 2020/02/06 06:00
PHST- 2020/02/06 06:00 [entrez]
PHST- 2020/02/06 06:00 [pubmed]
PHST- 2020/07/17 06:00 [medline]
AID - ERC-18-0420 [pii]
AID - 10.1530/ERC-18-0420 [doi]
PST - epublish
SO  - Endocr Relat Cancer. 2019 Mar 1;26(3):R109-R130. doi: 10.1530/ERC-18-0420.