E7386, a Selective Inhibitor of the Interaction between β-Catenin and CBP, Exerts Antitumor Activity in Tumor Models with Activated Canonical Wnt Signaling

Abstract The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and the of multiple types cancer, its aberrant activation provides cancer cells with escape mechanisms from immune checkpoint inhibitors. E7386, an orally active selective inhibitor interaction between β-catenin CREB binding protein, which is part pathway, disrupts HEK293 adenomatous polyposis coli (APC)-mutated human gastric ECC10 cells. It also inhibited tumor growth xenograft model suppressed polyp formation intestinal tract ApcMin/+ mice, mutation Apc activates pathway. E7386 demonstrated antitumor activity against mouse mammary tumors developed virus (MMTV)-Wnt1 transgenic mice. Gene expression profiling using RNA sequencing data MMTV-Wnt1 tissue mice treated showed that downregulated genes hypoxia responses related to CCL2, IHC analysis induced infiltration CD8+ into tissues. Furthermore, synergistic combination anti-PD-1 antibody. In conclusion, demonstrates clear via modulation alteration microenvironments, can be enhanced Significance: These findings demonstrate novel anticancer agent, modulates signaling, altering microenvironment exhibiting