Repurposing the selective estrogen receptor modulator bazedoxifene to suppress gastrointestinal cancer growth.

ABSTRACT: Excessive signaling through gp130, the shared receptor for the interleukin (IL)6 family of cytokines, is a common hallmark in solid malignancies and promotes their progression. Here, we established the in vivo utility of bazedoxifene, a steroid analog clinically approved for the treatment of osteoporosis, to suppress gp130-dependent tumor growth of the gastrointestinal epithelium. Bazedoxifene administration reduced gastric tumor burden in gp130^Y757F mice, where tumors arise exclusively through excessive gp130/STAT3 signaling in response to the IL6 family cytokine IL11. Likewise, in mouse models of sporadic colon and intestinal cancers, which arise from oncogenic mutations in the tumor suppressor gene Apc and the associated β-catenin/canonical

SUBMITTER: Thilakasiri P 

PROVIDER: S-EPMC6460354 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature