哺乳动物雷帕霉素受体选择性抑制剂用于非小细胞肺癌靶向治疗

Mammalian Target of Rapamycin Inhibitors for the Targeted Therapy of Non-small Cell Lung Cancer

哺乳动物雷帕霉素受体(mTOR)是一种调控翻译启动的重要分子,以雷帕霉素对mTOR进行抑制,会诱发其上游磷脂酰肌醇3激酶/丝苏氨酸蛋白激酶Akt、丝裂原激活蛋白激酶或胞外信号调节激酶激酶/胞外信号调节激酶等细胞存活信号传导路径的反馈激活而导致肿瘤细胞对雷帕霉素耐药。但同时肿瘤细胞有可能对这些生存信号传导路径更加依赖,即更加"成瘾"。若将雷帕霉素与针对这些路径的靶向药物联用,可能进一步提高抗肿瘤的疗效。本文以非小细胞肺癌为侧重对象,介绍了mTOR抑制剂靶向治疗的临床进展。

The mammalian target of rapamycin (mTOR),a master regulator of translation initiation,has recently emerged as an attractive therapeutic target for cancer therapy.It has been demonstrated that mTOR inhibitors activate several cell survival pathways including phosphatidyl inositol 3-kinase/serine or threonine-specific protein kinase Akt and mitogen-activated protein kinase or extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase while suppressing mTOR signaling in different types ...