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晚期胃癌的当前分子靶向治疗:治疗机制、临床试验及实际应用的全面综述

Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application.

作者信息

Li Kaichun, Li Jin

机构信息

Tianyou Hospital, Tongji University, Shanghai 200331, China.

Tianyou Hospital, Tongji University, Shanghai 200331, China; Fudan University Shanghai Cancer Center, Shanghai Medical College, Department of Medical Oncology, Shanghai 200032, China.

出版信息

Gastroenterol Res Pract. 2016;2016:4105615. doi: 10.1155/2016/4105615. Epub 2016 Jan 10.

Abstract

Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.

摘要

尽管胃癌治疗取得了巨大进展,但它仍是全球癌症死亡的第三大主要原因。患者常常错过手术治愈的机会,因为癌症在确诊时已发展为晚期。与最佳支持治疗相比,化疗可改善生活质量并延长生存时间,但总体生存期往往较短。由于对胃癌的分子研究,新的分子靶向药物已进入临床应用。曲妥珠单抗,一种靶向人表皮生长因子受体2(HER2)的抗体,可显著提高HER2过表达的晚期胃癌患者的生存率。雷莫西尤单抗,一种靶向VEGFR-2的抗体,单独或与紫杉醇联合用于晚期胃癌的二线治疗,已被证明具有有益效果。VEGFR-2酪氨酸激酶抑制剂阿帕替尼可改善二线化疗失败后的晚期胃癌患者的生存率。不幸的是,靶向EGFR的抗体(西妥昔单抗或帕尼单抗)、靶向VEGF的单克隆抗体(贝伐单抗)、mTOR抑制剂(依维莫司)或靶向HGF/MET通路的药物均未显示出显著的生存获益。许多基于分子标志物的其他临床试验正在进行中。本综述将总结晚期胃癌的靶向治疗。

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