Trk Receptor Expression and Inhibition in Neuroblastomas
Neuroblastoma, the most common and deadly solid tumor in children, exhibits heterogeneous clinical behavior, from spontaneous regression to relentless progression. Current evidence suggests that the TRK family of neurotrophin receptors plays a critical role in these diverse behaviors. Neuroblastomas...
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Published in | Clinical cancer research Vol. 15; no. 10; pp. 3244 - 3250 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
15.05.2009
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Subjects | |
Online Access | Get full text |
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Summary: | Neuroblastoma, the most common and deadly solid tumor in children, exhibits heterogeneous clinical behavior, from spontaneous
regression to relentless progression. Current evidence suggests that the TRK family of neurotrophin receptors plays a critical role in these diverse behaviors. Neuroblastomas expressing TrkA are biologically
favorable and prone to spontaneous regression or differentiation, depending on the absence or presence of its ligand (NGF)
in the microenvironment. In contrast, TrkB-expressing tumors frequently have MYCN amplification and are very aggressive and often fatal tumors. These tumors also express the TrkB ligand (BDNF), resulting
in an autocrine or paracrine survival pathway. Exposure to BDNF promotes survival, drug resistance, and angiogenesis of TrkB-expressing
tumors. Here we review the role of Trks in normal development, the different functions of Trk isoforms, and the major Trk
signaling pathways. We also review the roles these receptors play in the heterogeneous biological and clinical behavior of
neuroblastomas, and the activation of Trk receptors in other cancers. Finally we address the progress that has been made in
developing targeted therapy with Trk-selective inhibitors to treat neuroblastomas and other tumors with activated Trk expression. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-08-1815 |