In order to explore the functional relevance of this overexpression for mediating treatment resistance, Kendziorra and colleagues recently silenced TCF4 in resistant colorectal cancer cell lines and could show that RNAi-mediated inhibition of TCF4 caused a significant radiosensitization of colorectal cancer cells with high TCF reporter activity (Fig. 1). This evidence concerns the gene HNF4A and colorectal cancer.