Abstract
AREAS COVERED: This perspective discusses the challenges of targeting the Wnt signaling cascade, the safety, efficacy, and therapeutic potential of specific CBP/β-catenin antagonists and a rationale for the pleiotropic effects of CBP/β-catenin antagonists beyond Wnt signaling. EXPERT OPINION: CBP/β-catenin antagonists can correct lineage infidelity, enhance wound healing, both normal and aberrant (e.g. fibrosis) and force the differentiation and lineage commitment of stem cells and cancer stem cells by regulating enhancer and super-enhancer coactivator occupancy. Small molecule CBP/β-catenin antagonists rebalance the equilibrium between CBP/β-catenin versus p300/β-catenin dependent transcription and may be able to treat or prevent many diseases of aging, via maintenance of our somatic stem cell pool, and regulating mitochondrial function and metabolism involved in differentiation and immune cell function.