Targeting Wnt Signaling in Colon Cancer Stem Cells

The identification of cancer stem cell (CSC) populations in virtually all tumor types has widespread clinical consequences. CSCs are suggested to be the only cells within malignancies endowed with tumorigenic capacity and are, therefore, directly implicated in therapy resistance and minimal residual disease. The genetic and molecular mechanisms sustaining CSCs are only currently emerging. For instance, aberrant activation of the Wnt signaling pathway is crucial for many cancer types and especially those of the gastrointestinal tract. Indeed, Wnt signaling activity was shown to designate colon CSCs and is, therefore, an attractive target for new therapeutics. Here, we review some of the latest developments that have been achieved to inhibit the Wnt pathway in the context of colon CSCs. Moreover, we discuss some of the pitfalls that can be anticipated and present new opportunities for therapeutic intervention. Clin Cancer Res; 17(4); 647-53. (C) 2010 AACR.