Specifically, we and others have previously shown that genetic deletion or pharmacologic inhibition of downstream effectors of β-catenin-TCF/LEF interactions, such as cyclin D1 (encoded by CCND1)57, GS16, mTORC121, TBX317, AXIN258, or TNFRSF1959 either result in partial tumor responses or compensatory negative feedback loops leading to enhanced tumorigenesis. The gene discussed is HNF4A; the disease is neoplasm.