Molecular predicators of duodenal familial adenomatous polyposis chemoprevention: Do chemopreventive drugs hit their presumed molecular targets?

Abstract

Patients with familial adenomatous polyposis (FAP) have an increased risk of developing duodenal adenomas and adenocarcinomas. In previous trials, sulindac (a cyclooxygenase inhibitor) alone failed to significantly suppress duodenal tumorigenesis in FAP patients, but sulindac plus the tyrosine kinase inhibitor erlotinib significantly reduced duodenal polyp burden. Delker and colleagues report in this issue (beginning on page 4) on transcriptome analyses that aimed to identify the molecular targets mediating the response to sulindac-erlotinib. Their exploratory transcriptome analyses suggested that sulindac-erlotinib suppressed duodenal polyposis via inhibiting Wnt/β-catenin, EGFR, and cyclooxygenase pathways. This perspective discusses the significance and limitations of the study.