Joyce FanFollow

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Colorectal cancer is one of the most common cancers worldwide. Understanding the mechanisms of colorectal cancer progression is crucial for the development of effective therapeutics. Epithelial-to-mesenchymal transition is a hallmark feature of cancer and is defined as the loss of epithelial cell features, such as apical-basal polarity and high expression of cell adhesion molecules, and the development of mesenchymal features, such as lack of polarity and increased cell mobility. Epithelial-to-mesenchymal is essential for cell migration, proliferation, and tumor growth. Both the TGF-β and SMAD pathway are associated with colorectal cancer progression. TGF-β is crucial to the cellular mechanism of cell differentiation and regulation. LY210976, a TGF-β inhibitor, has been proposed as a potential therapeutic for metastasis. The three studies reviewed here collectively demonstrated that LY2109761 is effective in reducing cell migration, invasion, and metastasis in mice and rabbit models. Combined with transcatheter arterial chemoembolization, inhibition of LY2109761 led to increased E-cadherin expression, indicating the maintenance of the epithelial cell phenotype, and suppressed tumor growth in rabbits. Together, these results suggest that LY2109761 is a strong candidate for inhibiting colorectal cancer spread. Future studies should continue to explore LY2109761 in preventing metastasis, especially in combination therapies in humans.