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Translational Diagnostics and Therapeutics in Pancreatic Neuroendocrine Tumors.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2016 Oct 15; Vol. 22 (20), pp. 5022-5029. - Publication Year :
- 2016
-
Abstract
- Pancreatic neuroendocrine tumors (PNET) are rare tumors, but have been increasing in incidence. Although typically thought of as indolent, more than half of patients present with metastatic disease. For many years, the only mutations commonly known in these tumors were those in the MEN1 gene. Recently, the genetics underlying PNETs have been further defined through exome sequencing. The most frequent alterations found in sporadic PNETs are in MEN1, DAXX/ATRX, and a variety of genes in the mTOR pathway. Confirmation of these mutations has prompted trials with a number of drugs active in these pathways, and two drugs were eventually approved in 2011-sunitinib and everolimus. New data additionally identify the MET and CD47 receptors as potential novel drug targets. Yet despite improvements in progression-free survival with sunitinib and everolimus, further studies defining when to use these agents and factors associated with limitations in their utility are needed. As more discoveries are made in the laboratory that elucidate additional molecular mechanisms important in the initiation and metastasis of PNETs, continued efforts to translate these discoveries into distinct new therapies will be needed to improve patient survival. Clin Cancer Res; 22(20); 5022-9. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS REVISING PARADIGMS".<br />Competing Interests: of Potential Conflicts of Interest No potential conflicts of interest were disclosed.<br /> (©2016 American Association for Cancer Research.)
- Subjects :
- CD47 Antigen genetics
Everolimus therapeutic use
Humans
Indoles therapeutic use
Neuroendocrine Tumors genetics
Pancreatic Neoplasms genetics
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins c-met genetics
Pyrroles therapeutic use
Sunitinib
TOR Serine-Threonine Kinases genetics
Angiogenesis Inhibitors therapeutic use
Antineoplastic Agents therapeutic use
Neuroendocrine Tumors drug therapy
Neuroendocrine Tumors pathology
Pancreatic Neoplasms drug therapy
Pancreatic Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 22
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Review
- Accession number :
- 27742788
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-16-0435