Development of novel biomarker for cetuximab therapy in lung cancer

抗egfr单克隆抗体西妥昔单抗（cetuximab）已被开发为一种新的肺癌分子靶向治疗药物。在这项研究中，我们开发了一种新的西妥昔单抗生物标志物，以选择将显示有意义的临床反应的患者亚群，利用我们最初的发现，西妥昔单抗的主要抗癌机制是免疫抗肿瘤活性，如抗体依赖性细胞毒性（ADCC）。因此，我们发现ULBP2是最重要的NKG2D配体，被称为NK细胞的激活配体，ULBP2的可溶性形式（sULBP2）直接抑制宿主NK细胞的细胞溶解活性和西妥昔单抗诱导的ADCC活性。因此，对于sULBP水平较低的患者，或手术后或化疗后sULBP2水平较低的患者给予西妥昔单抗治疗是西妥昔单抗治疗肺癌的最佳策略。

An anti-EGFR monoclonal antibody, cetuximab, has been developed as a novel molecular targeting therapy in lung cancer. In this study, we developed a novel biomarker for cetuximab to select the subset of patients who will show a meaningful clinical response, by using our original finding that the main anti-cancer mechanism of cetuximab is immunological antitumor activity such as antibody-dependent cellular cytotoxicity(ADCC). As a result, we revealed that ULBP2 is the most significant NKG2D ligands, which are known as the activating ligands of NK cells, and that soluble form of ULBP2(sULBP2) directly suppresses both the cytolytic activity and cetuximab induced ADCC activity of host NK cells. Therefore, administration of cetuximab to the patients with low levels of sULBP, or the patients after surgery or chemotherapy with lowest sULBP2 levels is the best strategy for cetuximab treatment for lung cancer.