γ-secretase inhibitors (GSIs) block Notch pathway activation, which is thought to contribute to various epithelial cancers. Previous studies in the Apcmin mouse model of colon cancer suggest that GSIs inhibit intestinal neoplasia by converting proliferating cells into terminally differentiated goblet cells. Droy-Dupré et al. now assess the effects of a GSI called dibenzazepine (DBZ) in the intestines of healthy mice. They show that DBZ induces a homogenous goblet-cell conversion throughout the intestine, but that effects on intestinal-crypt-cell proliferation are heterogeneous. The authors propose that the effects of GSIs cannot be determined by goblet-cell conversion alone and encourage caution in the use of DBZ as a therapy. Page 107
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