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Angiogenesis in Neuroendocrine Tumors: Therapeutic Applications.
MedLine Citation:
PMID:  22538258     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The considerable research efforts devoted to the understanding of the mechanisms of tumor angiogenesis have resulted in the development of targeted anti-angiogenic therapies and finally in their introduction in clinical practice. Neuroendocrine tumors (NETs), which are characterized by a high vascular supply and a strong expression of VEGF-A, one of the most potent pro-angiogenic factors, are an attractive indication for these new treatments. However, several lines of evidence show that the dense vascular networks associated with low-grade NETs are more likely to be a marker of differentiation than a marker of aggressiveness, as in other epithelial tumors. These observations form the basis for the so-called 'neuroendocrine paradox', according to which the most vascularized are the most differentiated and the less angiogenic NETs. This must be kept in mind when discussing the role of anti-angiogenic strategies in the treatment of NETs. Nevertheless, several targeted therapies, with direct or indirect anti-angiogenic properties, including anti-VEGF antibodies, tyrosine kinase inhibitors (sunitinib) and mTOR inhibitors (everolimus), have recently proven to be of clinical benefit. In addition, some drugs already used in NET treatment, such as somatostatin analogues and interferon-α, may also have anti-angiogenic properties. The main challenges for the next future are to validate biomarkers for the selection of patients and the prediction of their response to refine the indications of anti-angiogenic targeted therapies and to overcome the mechanisms of resistance, which explain the limited duration of action of most of these treatments.
Authors:
Jean-Yves Scoazec
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-25
Journal Detail:
Title:  Neuroendocrinology     Volume:  -     ISSN:  1423-0194     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0035665     Medline TA:  Neuroendocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Affiliation:
Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Anatomie Pathologique, et Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Lyon, France.
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