Neutralizing monoclonal antibody against Dickkopf2 impairs lung cancer progression activating NK cells.

Adenomatous polyposis coli () and proto-oncogene () mutations frequently co-occur in non-small cell lung cancer. Inactivating mutations in colorectal carcinoma has been well characterized, leading to the approaches targeting on dysregulated pathway. However, it remains undetermined whether such approaches are also applicable to non-small cell lung cancer patients harboring similar mutations of . Dickkopf-related protein 2 (DKK2) is a Wnt antagonist. Our previous study has proved that anti-DKK2 antibody 5F8 suppressed the growth of colorectal carcinoma with mutations, illustrating a new target agent of APC-mutated tumors. This study aimed to investigate the potential of applying anti-DKK2 antibody to non-small cell lung cancer with mutations. We found significant upregulation of Dkk2 expression in -mutated lung cancers. Administration of DKK2 antibody inhibited cancer growth modulating tumor immune microenvironment in lung cancer mouse models. Our study provided strong evidence supporting mutations-directed applications of anti-DKK2 targeted therapy in a wide range of cancer types, including lung cancer.