Wnt/β-catenin signaling in colorectal cancer: Is therapeutic targeting even possible?

Abstract

The Wnt/β-catenin signaling pathway has been implicated as the central mechanism that drives colorectal carcinogenesis. Its activation is historically due to mutation on APC (adenomatous polyposis coli), resulting to nuclear localization of β-catenin and expression of Wnt target genes that promote tumor progression. Although this pathway seems to be a pivotal therapeutic target because of its critical role in colorectal cancer, there has been no clinically approved therapies targeting Wnt/β-catenin signaling pathway to this date. Here, we reviewed the recent progress of this signal transduction pathway in colorectal tumorigenesis. Apart from their roles in cancer initiation, the new pathway modulators (activators and repressors) also participate in chemoresistance, epithelial-mesenchymal transition and cancer stem cell renewal. Of the proteins reported to modulate this pathway, CDX2 (Caudal-related homeobox transcription factor 2) showed potentials as promising molecular target. CDX2 warrants further studies to determine its significance as molecular target for colorectal cancer therapeutics. Overall, the regulation of Wnt/β-catenin signaling pathway remains intriguingly complex and is not fully understood in spite of the widespread research efforts. Its intricacy remains a major barrier in the development of chemotherapeutic agent that specifically targets it.

Keywords: Colorectal cancer; Wnt activators; Wnt repressors; Wnt signaling; β-catenin.