Chen Z, Li Y, Tan B, Zhao Q, Fan L, Li F, Zhao X
Graduate School of Hebei Medical University, Shijiazhuang, China.
The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Drugs Today (Barc). 2020 Jul;56(7):469-482. doi: 10.1358/dot.2020.56.7.3112071.
Gastric cancer is one of the most common malignant tumors in the world. In China, its morbidity and mortality are second only to lung cancer. Chemotherapy combined with targeted therapy brings survival benefits to patients with advanced gastric cancer. Targets for targeted therapy of gastric cancer include human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) and Claudin 18.2 (CLDN 18.2). The main challenge of tumor molecule-targeted drugs is resistance. The main mechanisms of drug resistance include tumor establishment of compensatory signaling pathways, target protein changes, tumor microenvironment changes, tumor heterogeneity and tumor adaptation to targeted drugs. The combined action of multiple drug resistance mechanisms promotes the development of targeted drug resistance. In order to attract the attention of researchers, this paper reviews the mechanisms of drug resistance in gastric cancer-targeted therapy. In addition, the research status of drug resistance in molecule-targeted therapy of gastric cancer is summarized. It is of great clinical significance to explore the drug resistance mechanisms of targeted drugs and reverse drug resistance in gastric cancer. Last, the future development of molecule-targeted therapy is prospected.
胃癌是世界上最常见的恶性肿瘤之一。在中国，其发病率和死亡率仅次于肺癌。化疗联合靶向治疗为晚期胃癌患者带来生存益处。胃癌靶向治疗的靶点包括人表皮生长因子受体（EGFR）、人表皮生长因子受体2（HER2）、血管内皮生长因子（VEGF）、雷帕霉素靶蛋白（mTOR）和紧密连接蛋白18.2（CLDN 18.2）。肿瘤分子靶向药物的主要挑战是耐药性。耐药的主要机制包括肿瘤建立代偿性信号通路、靶蛋白改变、肿瘤微环境变化、肿瘤异质性以及肿瘤对靶向药物的适应性。多种耐药机制的共同作用促进了靶向耐药的发展。为引起研究人员的关注，本文综述了胃癌靶向治疗中的耐药机制。此外，总结了胃癌分子靶向治疗中耐药性的研究现状。探索胃癌靶向药物的耐药机制并逆转耐药性具有重要的临床意义。最后，对分子靶向治疗的未来发展进行了展望。
