Advances in targeted therapy for gastric cancer based on tumor driver genes
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Feb 19;53(1):73-83.
doi: 10.3724/zdxbyxb-2023-0522.
[Article in
English,
Chinese]
Affiliations
- 1 College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, China. wushiying@zju.edu.cn.
- 2 Key Laboratory of Biosystems Homeostasis and Protection, Ministry of Education, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Zhejiang University, Hangzhou 310058, China. wushiying@zju.edu.cn.
- 3 Key Laboratory of Biosystems Homeostasis and Protection, Ministry of Education, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Zhejiang University, Hangzhou 310058, China. xupl@zju.edu.cn.
- 4 Institute of Intelligent Medicine, Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, China. xupl@zju.edu.cn.
- 5 Life Sciences Institute, Zhejiang University, Hangzhou 310058, China. xupl@zju.edu.cn.
- 6 Cancer Center, Zhejiang University, Hangzhou 310058, China. xupl@zju.edu.cn.
- 7 Key Laboratory of Biosystems Homeostasis and Protection, Ministry of Education, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Zhejiang University, Hangzhou 310058, China. zzff@zju.edu.cn.
- 8 Institute of Intelligent Medicine, Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, China. zzff@zju.edu.cn.
As the understanding of the pathogenic mechanisms of gastric cancer deepens and the identification of gastric cancer driver genes advances, drugs targeting gastric cancer driver genes have been applied in clinical practice. Among them, trastuzumab, as the first targeted drug for gastric cancer, effectively inhibits the proliferation and metastasis of tumor cells by targeting overexpressed human epidermal growth factor receptor 2 (HER2). Trastuzumab has become the standard treatment for HER2-positive gastric cancer patients. Ramucirumab, on the other hand, inhibits tumor angiogenesis by targeting vascular endothelial growth factor receptor 2 (VEGFR2) and has been used as second-line therapy for advanced gastric cancer patients. In addition, bemarituzumab targets overexpressed fibroblast growth factor receptor 2 (FGFR2), while zolbetuximab targets overexpressed claudin 18.2 (CLDN18.2), significantly extending progression-free survival and overall survival in patients with gastric cancer in clinical trials. This article reviews the roles of tumor driver genes in the progression of gastric cancer, and the treatment strategies for gastric cancer primarily based on targeting HER2, VEGF, FGFR2, CLDN18.2 and MET. This provides a reference for clinical application of targeted therapy for gastric cancer.
随着胃癌致病机制深入解析及胃癌驱动基因的鉴定，靶向胃癌驱动基因的药物逐渐应用临床。其中，曲妥珠单抗作为首个胃癌靶向药物，通过靶向过表达的人表皮生长因子受体2（HER2）抑制肿瘤细胞的增殖、生存和转移等过程，已成为HER2阳性胃癌患者的一线治疗药物。雷莫芦单抗则通过靶向血管内皮生长因子受体2（VEGFR2）抑制肿瘤血管生成，用于晚期胃癌患者的二线治疗。此外，贝马利珠单抗和佐妥昔单抗分别靶向过度表达的成纤维细胞生长因子受体2（FGFR2）和紧密连接蛋白18.2 （CLDN18.2），在临床试验中显著延长胃癌患者的无进展生存期和总生存期。本文回顾了靶向HER2、VEGF、FGFR2、 CLDN18.2和MET 等肿瘤驱动基因的胃癌治疗策略，介绍了肿瘤驱动基因在胃癌进程中的作用及其靶向药物的应用，以期为胃癌靶向治疗药物的研发和临床应用提供参考。.
Keywords:
Clinical trials; Gastric cancer; Review; Targeted therapy; Tumor driver genes.
MeSH terms
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Claudins / therapeutic use
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Humans
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Molecular Targeted Therapy
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Ramucirumab
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Receptor, ErbB-2
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Stomach Neoplasms* / drug therapy
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Stomach Neoplasms* / genetics
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Trastuzumab / therapeutic use
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Vascular Endothelial Growth Factor A
Substances
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Vascular Endothelial Growth Factor A
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Trastuzumab
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Receptor, ErbB-2
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Ramucirumab
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CLDN18 protein, human
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Claudins