Development of molecular targeted therapy for lung cancer metastasis considering characteristics of organ microenvironment

我们关注肿瘤微环境，发现抑制破骨细胞功能的药物抑制肺癌骨转移。在骨转移灶中选择性表达的因子可作为多器官转移的抑制剂。树突状细胞产生可溶性VEGF受体1，抑制血管生成，从而抑制肺癌进展。人源化抗HM 1.24抗体抑制表达HM 1.24的肺癌细胞的生长。肝细胞生长因子（HGF）可诱导对EGFR酪氨酸激酶抑制剂的耐药，提示HGF可能是克服肺癌耐药的重要靶点。

We focused on cancer microenvironment and found that drugs which suppressed osteoclast-function inhibited lung cancer bone metastasis. The factor selectively expressed in bone metastatic lesions acted as an inhibitor of multiple organ metastasis. Dendritic cells produced soluble VEGF receptor 1, suppressed angiogenesis, and thereby inhibited lung cancer progression. Humanized anti-HM1.24 antibody inhibited growth of HM1.24 expressing lung cancer cells. Hepatocyte growth factor (HGF) induced resistance to EGFR tyrosine kinase inhibitors, indicating that HGF may be important target for overcoming the resistance in lung cancer.