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.
Sandra W. Ryeom
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