The cautionary tale of side effects of chronic Notch1 inhibition

Aberrant Notch1 signaling is implicated in several types of cancer. Therefore, Notch signaling pathways are important anticancer targets. Pan-Notch receptor inhibition is associated with numerous complications; thus, selective Notch receptor inhibition has been pursued. Studies have shown minimal si...

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Bibliographic Details
Published in:The Journal of clinical investigation 2011-02, Vol.121 (2), p.508-509
Main Author: Ryeom, Sandra W
Format: Article
Language:English
Subjects:
Animals
Biomedical research
Humans
Intracellular Signaling Peptides and Proteins
Membrane Proteins - metabolism
Mice
Receptor, Notch1 - antagonists & inhibitors
Signal Transduction - physiology
Vascular Neoplasms - metabolism
Vascular Neoplasms - pathology
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Summary:Aberrant Notch1 signaling is implicated in several types of cancer. Therefore, Notch signaling pathways are important anticancer targets. Pan-Notch receptor inhibition is associated with numerous complications; thus, selective Notch receptor inhibition has been pursued. Studies have shown minimal side effects with short-term blockade of either Notch1 or its ligand Delta-like 4, but long-term side effects were not investigated. In this issue of the JCI, Liu et al. use mouse models to demonstrate the consequence of long-term Notch1 inhibition. They present evidence that chronic Notch1 inhibition leads to vascular tumors in the liver and decreased survival, which suggests that Notch1 therapies should be reevaluated.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI45976