Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200062, China.
Anticancer Agents Med Chem. 2013 Feb;13(2):276-80. doi: 10.2174/1871520611313020014.
Mesothelin, a glycosylphosphatidylinositol (GPI) anchored cell surface protein, is a potential target for antibody-based cancer therapy due to its high expression in mesothelioma, ovarian cancer, pancreatic cancer, cholangiocarcinoma and other cancers. The SS1P immunotoxin and MORAb-009 (amatuximab), a chimeric monoclonal antibody, are currently being evaluated in clinical trials. In this review, we discuss the role of mesothelin in cancer progression and provide new insights into mesothelin-targeted cancer therapy. Recent studies highlight three mechanisms by which mesothelin plays a role in cancer progression. First, mesothelin may aid in the peritoneal implantation and metastasis of tumors through its interaction with mucin MUC16 (also known as CA125). Second, mesothelin may promote cancer cell survival and proliferation via the NF-κB signaling pathway. Finally, mesothelin expression promotes resistance to certain chemotherapy drugs such as TNF-α, paclitaxel, and a combination of platinum and cyclophosphamide. However, its cancerspecific expression makes mesothelin a potential target for monoclonal antibody therapy. New human monoclonal antibodies targeting mesothelin have been isolated by phage display technology and may provide opportunities for novel cancer therapy.
间皮素是一种糖基磷脂酰肌醇（GPI）锚定的细胞表面蛋白，由于其在间皮瘤、卵巢癌、胰腺癌、胆管癌和其他癌症中的高表达，成为抗体为基础的癌症治疗的潜在靶点。SS1P 免疫毒素和 MORAb-009（amatuximab），一种嵌合单克隆抗体，目前正在临床试验中进行评估。在这篇综述中，我们讨论了间皮素在癌症进展中的作用，并为间皮素靶向癌症治疗提供了新的见解。最近的研究强调了间皮素在癌症进展中发挥作用的三种机制。首先，间皮素可能通过与其相互作用的黏蛋白 MUC16（也称为 CA125）来帮助肿瘤在腹膜中的植入和转移。其次，间皮素可能通过 NF-κB 信号通路促进癌细胞的存活和增殖。最后，间皮素的表达促进了对某些化疗药物的耐药性，如 TNF-α、紫杉醇以及铂类和环磷酰胺的联合用药。然而，由于其癌症特异性表达，间皮素成为单克隆抗体治疗的潜在靶点。通过噬菌体展示技术分离出的针对间皮素的新型人源单克隆抗体可能为新型癌症治疗提供机会。
