Theoretical basis validation and oxidative stress markers for cancer prevention clinical trials of aspirin

Abstract

Aspirin, a nonsteroidal anti-inflammatory drug, has been proven effective in a clinical trial of carcinogenesis blockade. However, various modes of action have been reported for these effects. Thus, in this study, we aimed to present reasonable mode of actions as a proof of concept for human trials, especially trials for patients with familial adenomatous polyposis (FAP). Aspirin treatment at 1000 ppm inhibited intestinal tumorigenesis in FAP model Min mice. As a mode of action, aspirin regulated β-catenin signaling, inflammation, and oxidative stress both in vivo and in vitro. Furthermore, we examined novel markers predictive of aspirin treatment based on liquid biopsy. Here, we demonstrated that aspirin reduced the levels of reactive carbonyl species in the serum of Min mice. These data are expected to be of use for proof of concept of aspirin human trials and implied for the prediction of aspirin efficacy.