Adenomatous polyposis coli (APC) and KRAS proto-oncogene (KRAS) mutations frequently co-occur in non-small cell lung cancer. Inactivating APC mutations in colorectal carcinoma has been well characterized, leading to the approaches targeting on dysregulated APC pathway. However, it remains undetermined whether such approaches are also applicable to non-small cell lung cancer patients harboring similar mutations of APC. 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 APC 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 APC mutations. We found significant upregulation of Dkk2 expression in APC-mutated lung cancers. Administration of DKK2 antibody inhibited cancer growth via modulating tumor immune microenvironment in lung cancer mouse models. Our study provided strong evidence supporting APC mutations-directed applications of anti-DKK2 targeted therapy in a wide range of cancer types, including lung cancer.

腺瘤性大肠杆菌 ( APC ) 和KRAS原癌基因 ( KRAS ) 突变经常在非小细胞肺癌中同时发生。结直肠癌中APC失活突变已得到很好的表征，从而产生了针对失调的APC通路的方法。然而，目前尚不确定这些方法是否也适用于携带类似APC突变的非小细胞肺癌患者。 Dickkopf 相关蛋白 2 (DKK2) 是一种 Wnt 拮抗剂。我们前期的研究证明抗DKK2抗体5F8可以抑制APC突变结直肠癌的生长，为APC突变肿瘤提供了新的靶点。本研究旨在探讨抗 DKK2 抗体应用于APC突变非小细胞肺癌的潜力。我们发现APC突变肺癌中 Dkk2 表达显着上调。在肺癌小鼠模型中，施用 DKK2 抗体可通过调节肿瘤免疫微环境来抑制癌症生长。我们的研究提供了强有力的证据，支持APC突变导向的抗 DKK2 靶向治疗在多种癌症类型（包括肺癌）中的应用。