Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Cancers (Basel). 2014 Jul 7;6(3):1441-63. doi: 10.3390/cancers6031441.
The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key signaling pathways induced by various receptor-tyrosine kinases. Accumulating evidence shows that this pathway is an important promoter of cell growth, metabolism, survival, metastasis, and resistance to chemotherapy. Genetic alterations in the PI3K/Akt/mTOR pathway in gastric carcinoma have often been demonstrated. Many kinds of molecular targeting therapies are currently undergoing clinical testing in patients with solid tumors. However, with the exception of the ErbB2-targeting antibody, targeting agents, including PI3K/Akt/mTOR inhibitors, have not been approved for treatment of patients with gastric carcinoma. This review summarizes the current knowledge on PI3K/Akt/mTOR signaling in the pathogenesis of gastric carcinoma and the possible therapeutic targets for gastric carcinoma. Improved knowledge of the PI3K/Akt/mTOR pathway in gastric carcinoma will be useful in understanding the mechanisms of tumor development and for identifying ideal targets of anticancer therapy for gastric carcinoma.
磷脂酰肌醇 3-激酶(PI3K)/Akt/雷帕霉素靶蛋白(mTOR)通路是多种受体酪氨酸激酶诱导的关键信号通路之一。越来越多的证据表明,该通路是细胞生长、代谢、存活、转移和化疗耐药的重要促进因素。在胃癌中已经经常证明 PI3K/Akt/mTOR 通路的遗传改变。目前正在对实体瘤患者进行多种针对分子靶点的治疗的临床试验。然而,除了针对 ErbB2 的抗体靶向药物外,包括 PI3K/Akt/mTOR 抑制剂在内的靶向药物尚未被批准用于治疗胃癌患者。这篇综述总结了目前关于 PI3K/Akt/mTOR 信号通路在胃癌发病机制中的作用及其作为胃癌治疗靶点的可能性。对胃癌中 PI3K/Akt/mTOR 通路的深入了解将有助于理解肿瘤发展的机制,并确定用于胃癌的抗癌治疗的理想靶点。