PMID- 23840053
OWN - NLM
STAT- MEDLINE
DCOM- 20130924
LR  - 20231004
IS  - 1460-2105 (Electronic)
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 105
IP  - 14
DP  - 2013 Jul 17
TI  - Current understanding of the molecular biology of pancreatic neuroendocrine 
      tumors.
PG  - 1005-17
LID - 10.1093/jnci/djt135 [doi]
AB  - Pancreatic neuroendocrine tumors (PanNETs) are complicated and often deadly 
      neoplasms. A recent increased understanding of their molecular biology has 
      contributed to expanded treatment options. DNA sequencing of samples derived from 
      patients with PanNETs and rare genetic syndromes such as multiple endocrine 
      neoplasia type 1 (MEN1) and Von Hippel-Lindau (VHL) syndrome reveals the 
      involvement of MEN1, DAXX/ATRX, and the mammalian target of rapamycin (mTOR) 
      pathways in PanNET tumorigenesis. Gene knock-out/knock-in studies indicate that 
      inactivation of factors including MEN1 and abnormal PI3K/mTOR signaling uncouples 
      endocrine cell cycle progression from the control of environmental cues such as 
      glucose, leading to islet cell overgrowth. In addition, accumulating evidence 
      suggests that further impairment of endothelial-endocrine cell interactions 
      contributes to tumor invasion and metastasis. Recent phase III clinical trials 
      have shown that therapeutic interventions, such as sunitinib and everolimus, 
      targeting those signal transduction pathways improve disease-free survival rates. 
      Yet, cure in the setting of advanced disease remains elusive. Further advances in 
      our understanding of the molecular mechanisms of PanNETs and improved preclinical 
      models will assist in developing personalized therapy utilizing novel drugs to 
      provide prolonged control or even cure the disease.
FAU - Zhang, Jianliang
AU  - Zhang J
AD  - Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 
      14263, USA.
FAU - Francois, Rony
AU  - Francois R
FAU - Iyer, Renuka
AU  - Iyer R
FAU - Seshadri, Mukund
AU  - Seshadri M
FAU - Zajac-Kaye, Maria
AU  - Zajac-Kaye M
FAU - Hochwald, Steven N
AU  - Hochwald SN
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20130709
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CDKN2C protein, human)
RN  - 0 (Co-Repressor Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p18)
RN  - 0 (DAXX protein, human)
RN  - 0 (Indoles)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Molecular Chaperones)
RN  - 0 (NOTCH1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Pyrroles)
RN  - 0 (Receptor, Notch1)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - RWM8CCW8GP (Octreotide)
RN  - V99T50803M (Sunitinib)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/drug effects/*metabolism
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Hypoxia
MH  - Co-Repressor Proteins
MH  - Cyclin-Dependent Kinase Inhibitor p18/metabolism
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Everolimus
MH  - Gene Knock-In Techniques
MH  - Gene Knockout Techniques
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Indoles/pharmacology
MH  - Islets of Langerhans/metabolism
MH  - Molecular Chaperones
MH  - Molecular Targeted Therapy
MH  - *Mutation/drug effects
MH  - Neovascularization, Pathologic/metabolism/prevention & control
MH  - Neuroendocrine Tumors/genetics/*metabolism
MH  - Nuclear Proteins/drug effects/*metabolism
MH  - Octreotide/pharmacology
MH  - Pancreatic Neoplasms/genetics/*metabolism
MH  - Proto-Oncogene Proteins/drug effects/*metabolism
MH  - Pyrroles/pharmacology
MH  - Receptor, Notch1/genetics
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/analogs & derivatives/pharmacology
MH  - Sunitinib
MH  - TOR Serine-Threonine Kinases/drug effects/*metabolism
PMC - PMC6281020
EDAT- 2013/07/11 06:00
MHDA- 2013/09/26 06:00
PMCR- 2014/07/13
CRDT- 2013/07/11 06:00
PHST- 2013/07/11 06:00 [entrez]
PHST- 2013/07/11 06:00 [pubmed]
PHST- 2013/09/26 06:00 [medline]
PHST- 2014/07/13 00:00 [pmc-release]
AID - djt135 [pii]
AID - 10.1093/jnci/djt135 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 2013 Jul 17;105(14):1005-17. doi: 10.1093/jnci/djt135. Epub 
      2013 Jul 9.