Preclinical leads for chemoprevention of colorectal cancer: novel strategies to regulate apoptosis and proliferation

PhD ceremony: Ms. D.M. Heijink, 14.45 uur, Academiegebouw, Broerstraat 5, Groningen

Title: Preclinical leads for chemoprevention of colorectal cancer: novel strategies to regulate apoptosis and proliferation

Promotor(s): prof. E.G.E. de Vries, prof. J.H. Kleibeuker

Faculty: Medical Sciences

Colorectal cancer is potentially preventable because it develops relatively slow via the premalignant stage of an adenoma. Prevention is especially worthwhile for individuals with an increased (genetic) risk for colorectal cancer. Non-steroidal anti-inflammatory drugs (NSAIDs) have already proven to exert chemopreventive effects. The novel therapeutic drug TRAIL can induce cell death (apoptosis) in transformed cells without affecting normal cells. The subject of this thesis was to investigate the effects of TRAIL and the NSAID sulindac for chemoprevention in models of colorectal adenomas. It was found that the combination of drugs induced more apoptosis than treatment with both single agents. The effect of the combination was dependent on activation of the Wnt-pathway, one of the most important biological pathways in colorectal carcinogenesis. Other potential targets for chemoprevention were also identified.