Cancer

Cell culture, mouse and patient sample studies suggest anti-FZD5 mAbs could help treat pancreatic, colorectal, and other RNF43-mutant cancers. In four RNF43-mutant human pancreatic ductal adenocarcinoma (PDAC) cell lines, two anti-FZD5 mAbs decreased cell viability compared with control IgG. In a xenograft mouse model of RNF43-mutant PDAC, one of the anti-FZD5 mAbs decreased tumor growth and mucin production in tumors - a marker of cellular differentiation. In two orthotopic xenograft mouse models of RNF43-mutant PDAC, the anti-FZD5 mAb decreased tumor growth compared with vantictumab or vehicle. In colorectal organoids derived from two patients with RNF43-mutant colorectal cancer, the antagonist mAb decreased viability compared with control IgG. Next steps include optimizing the specificity of the antibodies for FZD5...