Development of cancer treatment by molecular targeted anti-cancer hybrid peptide against refractory cancers which are resistant to cancer chemotherapy

我们专注于靶向转铁蛋白受体、IL 4受体α、神经纤毛蛋白-1和Her 2，这些受体在包括胰腺癌和胶质母细胞瘤在内的难治性癌细胞上过表达，并设计了杂合肽，其中靶向这些受体的肽与选择性分解癌细胞膜的裂解型肽缀合。发现设计的杂合肽在体外和体内对过表达这些受体的癌细胞（包括对曲妥珠单抗和拉帕替尼具有抗性的细胞系）具有有效的细胞毒性和抗肿瘤活性。因此，本研究中设计的杂合肽可能为未来难治性癌症患者提供有效的治疗选择。

We focused on the targeting to transferrin receptor, IL4 receptor alpha, Neuropilin-1, and Her2 which over-express on the refractory cancer cells including pancreatic cancer and glioblastoma, and designed hybrid peptide in which targeting peptides to these receptors were conjugated with lytic type peptide that disintegrates selectively cancer cell membrane. It was found that designed hybrid peptides had effective cytotoxic and anti-tumor activities toward cancer cells over-expressing these receptors including resistant cell lines to trastuzumab and lapatinib both in vitro and in vivo. Thus, it is suggested that hybrid peptide designed in this study may provide a potent therapeutic option for patients with refractory cancer in the future.