Luo Dong, Liu Yunmei, Lu Zhengmao, Huang Lei
Department of Gastroenterology, National Clinical Research Center for Digestive Diseases, The First Affiliated Hospital of Naval Medical University/Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.
Center of Structural Heart Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Mol Med. 2025 Feb 8;31(1):52. doi: 10.1186/s10020-025-01075-y.
Gastric cancer (GC) is one of the most common malignant tumors worldwide, and its treatment has been a focus of medical research. Herein we systematically review the current status of and advancements in targeted therapy and immunotherapy for GC, which have emerged as important treatment strategies in recent years with great potential, and summarize the efficacy and safety of such treatments. Targeted therapies against key targets in GC, including epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR), have shown remarkable therapeutic efficacies by inhibiting tumor progression and/or blood supply. In particular, markable breakthroughs have been made in HER2-targeting drugs for HER2-positive GC patients. To address intrinsic and acquired resistances to HER2-targeting drugs, novel therapeutic agents including bispecific antibodies and antibody-drug conjugates (ADC) targeting HER2 have been developed. Immunotherapy enhances the recognition and elimination of cancer cells by activating body anticancer immune system. Programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) antibodies are the most commonly used immunotherapeutic agents and have been used with some success in GC treatment. Innovative immunotherapy modalities, including adoptive immune cell therapy, tumor vaccines, and non-specific immunomodulators therapy, and oncolytic viruses have shown promise in early-stage clinical trials for GC. Clinical trials have supported that targeted therapy and immunotherapy can significantly improve the survival and quality of life of GC patients. However, the effects of such therapies need to be further improved and more personalized, with advancement in researches on tumor immune microenvironment. Further studies remain needed to address the issues of drug resistance and adverse events pertaining to such therapies for GC. The combined application of such therapies and individualized treatment strategies should be further explored with novel drugs developed, to provide more effective treatments for GC patients.
胃癌（GC）是全球最常见的恶性肿瘤之一，其治疗一直是医学研究的重点。在此，我们系统回顾了近年来已成为具有巨大潜力的重要治疗策略的GC靶向治疗和免疫治疗的现状与进展，并总结了这些治疗方法的疗效和安全性。针对GC关键靶点的靶向治疗，包括表皮生长因子受体（EGFR）、人表皮生长因子受体2（HER2）以及血管内皮生长因子（VEGF）/VEGF受体（VEGFR），通过抑制肿瘤进展和/或血液供应已显示出显著的治疗效果。特别是，针对HER2阳性GC患者的HER2靶向药物取得了显著突破。为解决对HER2靶向药物的内在和获得性耐药问题，已开发出包括双特异性抗体和靶向HER2的抗体药物偶联物（ADC）在内的新型治疗药物。免疫治疗通过激活机体抗癌免疫系统增强对癌细胞的识别和清除。程序性细胞死亡蛋白1（PD - 1）和程序性细胞死亡配体1（PD - L1）抗体是最常用的免疫治疗药物，在GC治疗中已取得一定成功。创新的免疫治疗模式，包括过继性免疫细胞治疗、肿瘤疫苗、非特异性免疫调节剂治疗以及溶瘤病毒，在GC的早期临床试验中已显示出前景。临床试验已证实靶向治疗和免疫治疗可显著提高GC患者的生存率和生活质量。然而，随着肿瘤免疫微环境研究的进展，此类治疗的效果仍需进一步改善并更加个体化。仍需进一步研究解决与GC此类治疗相关的耐药性和不良事件问题。应结合新药开发进一步探索此类治疗的联合应用和个体化治疗策略，以为GC患者提供更有效的治疗。
