Targeted therapies in gastric cancer and future perspectives
Targeted therapies in gastric cancer and future perspectives
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DOI：
10.3748/wjg.v22.i2.471
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发表时间：
2016-01-14
影响因子：
4.3
通讯作者：
Aksoy, Sercan
中科院分区：
文献类型：
--
作者：
Yazici, Ozan;Sendur, M. Ali Nahit;Aksoy, Sercan
晚期胃癌（AGC）与高死亡率相关，尽管有多种新的化疗选择，但AGC患者的生存率仍然很低。在发现靶向治疗方法后，研究集中在AGC的新治疗方案上。在过去的二十年中，许多针对AGC的靶向分子被开发出来。目前，已有两种靶向治疗分子被批准用于AGC患者。2010年，曲妥珠单抗作为一线联合治疗方案的一部分，成为首个显示可改善her2阳性AGC患者生存率的分子。2014年，ramucirumab是第二个提高生存率的靶向分子，被建议用于一线铂加氟嘧啶化疗后进展的AGC患者，无论是否接受蒽环类药物化疗。Ramucirumab是首个单药治疗晚期胃食管癌的靶向治疗药物。虽然这两种分子被引入临床应用，但许多其他有希望的分子已经在I - II期试验中进行了测试。很明显，在不久的将来，许多不同的靶向治疗将用于治疗AGC。本文将对AGC和胃食管结肿瘤的靶向治疗现状进行综述，包括HER（2-3）抑制剂、表皮生长因子受体抑制剂、酪氨酸激酶抑制剂、抗血管生成药物、c-MET抑制剂、哺乳动物雷帕霉素靶点抑制剂、针对其他分子通路的药物、成纤维细胞生长因子、cladin、胰岛素样生长因子、热休克蛋白和免疫治疗。
Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I - II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.