Experimental toolkit to study the oncogenic role of WNT signaling in colorectal cancer

Abstract

Colorectal cancer (CRC) is linked to the WNT/β-catenin signaling as its primary driver. Aberrant activation of WNT/β-catenin signaling is closely correlated with increased incidence, malignancy, poorer prognosis, and even higher cancer-related death. Research over the years has postulated various experimental models that have facilitated an understanding of the complex mechanisms underlying WNT signaling in CRC. In the present review, we have comprehensively summarized the in vitro, in vivo, patient-derived, and computational models used to study the role of WNT signaling in CRC. We discuss the use of CRC cell lines and organoids in capturing the molecular intricacies of WNT signaling and implementing xenograft and genetically engineered mouse models to mimic the tumor microenvironment. Patient-derived models, including xenografts and organoids, provide valuable insights into personalized medicine approaches. Additionally, we elaborated on the role of computational models in simulating WNT signaling dynamics and predicting therapeutic outcomes. By evaluating the advantages and limitations of each model, this review highlights the critical contributions of these systems to our understanding of WNT signaling in CRC. We emphasize the need to integrate diverse model systems to enhance translational research and clinical applications, which is the primary goal of this review.