The present invention relates to the biomarker TFF-3 that measures .gamma.-secretase mediated Notch processing. TFF-3 has utility in predicting and/or determining in vivo Notch-related toxicity associated with inhibition of Notch processing mediated by .gamma.-secretase. The reagents and methods of the invention can be utilized before, after, or concurrently with, pre-clinical, clinical, and/or post-clinical testing. The reagents and methods of the invention can be used to identify and maintain preferred doses of test compounds and thereby prevent medical complications, such as gastrointestinal cellular damage.