Cancer prevention is generally perceived as a long‐term process and is inevitably associated with adverse effects. Here, we report the development of a therapy‐like chemoprevention procedure that specifically targets premalignant tumor cells for apoptosis. This procedure is based on our finding that a deficiency in the adenomatous polyposis coli (APC) gene and subsequent activation of β‐catenin lead to the repression of cellular caspase‐8 (FLICE)‐like inhibitory protein (cFLIP) expression through activation of c‐Myc and that 9‐cis‐retinyl acetate (RAc) independently upregulates tumor necrosis factor alpha‐related apoptosis‐inducing ligand (TRAIL) death receptors and suppresses decoy receptors. Thus, the combination of TRAIL and RAc induces apoptosis in APC‐deficient premalignant cells without affecting normal cells in vitro. We also show that in APC+/Min mice, TRAIL and RAc synergistically induce apoptosis specifically in intestinal polyps. Short‐term non‐treatment strongly inhibit tumor growth and promote survival. We further show that TRAIL and RAc have no detrimental effect on stem cells and TRAIL and RAc treatment induces significant cell death in human colon polyps. These results support that TRAIL and RAc represent a potential selective therapeutic approach for colon cancer chemoprevention by targeting APC‐deficient cells for apoptosis.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B81.