晚期胃癌治疗的研究进展与未来方向
Research Progress and Future Treatment of Advanced Gastric Cancer
DOI: 10.12677/ACM.2022.125654, PDF,   
作者: 李艳芳：青海大学研究生院，青海 西宁；姬发祥*：青海大学附属医院，青海 西宁
关键词: 胃癌；免疫治疗；免疫检查点抑制剂；靶向治疗；Gastric Cancer； Immunotherapy； Immune Checkpoint Inhibitors； Targeted Therapy
摘要: 中国是胃癌高发国家，其中晚期患者占比高，生存率低。近年来，胃癌领域免疫治疗的研究成为主流方向，主要是程序性死亡受体(PD-1)等免疫检查点抑制剂，为胃癌的治疗打开了新世界的大门。随着肿瘤分子生物学的不断深入，越来越多的新靶点不断被发现，随之出现的新药物也给晚期胃癌的治疗带来了新的方向。本文将对目前临床前实验、临床试验的数据进行分析整理对晚期胃癌免疫治疗、靶向治疗等研究进展进行综述，并简单阐述晚期胃癌治疗的未来探索方向。
Abstract: China is a country with a high incidence of gastric cancer, in which the proportion of advanced pa-tients is high and the survival rate is low. In recent years, the research of immunotherapy in gastric cancer has become the main direction, mainly PD-1 and other immune checkpoint inhibitors, which opens a new world for the treatment of gastric cancer. With the development of tumor molecular biology, more and more new targets have been found, and the new drugs have brought new oppor-tunities for the treatment of advanced gastric cancer. In this paper, the data of preclinical and clini-cal trials are analyzed and integrated, and the research progress of immunotherapy and targeted therapy for advanced gastric cancer is reviewed. The future directions of the treatment of advanced gastric cancer were also briefly discussed.
文章引用：李艳芳, 姬发祥. 晚期胃癌治疗的研究进展与未来方向[J]. 临床医学进展, 2022, 12(5): 4523-4529. https://doi.org/10.12677/ACM.2022.125654

参考文献

[1] World Health Organization (2020) World Cancer Report 2020. World Health Organization, Geneva.
https://www.iarc.fr/cards_page/world-cancer-report/
[2] Chen, W., Zheng, R., Baade, P.D., Zhang, S., Zeng, H., Bray, F., et al. (2016) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66, 115-132. [Google Scholar] [CrossRef] [PubMed]
[3] Amin, M.B., Edge, S., Greene, F., et al. (2017) AJCC Cancer Staging Manual. Springer International Publishing, New York, 203-220.
[4] Wagner, A.D., Syn, N.L., Moehler, M., Grothe, W., Yong, W.P., Tai, B.C., et al. (2017) Chemotherapy for Advanced Gastric Cancer. Cochrane Database of Systematic Reviews, No. 8, Article No. CD004064. [Google Scholar] [CrossRef] 
[5] Leng, C., Li, Y., Qin, J., Ma, J., Liu, X., Cui, Y., et al. (2016) Relationship between Expression of PD-L1 and PD-L2 on Esophageal Squamous Cell Carcinoma and the An-ti-Tumor Effects of CD8+ T Cells. Oncology Reports, 35, 699-708. [Google Scholar] [CrossRef] [PubMed]
[6] Hughes, P.E., Caenepeel, S. and Wu, L.C. (2016) Targeted Therapy and Checkpoint Immunotherapy Combinations for the Treatment of Cancer. Trends in Immunology, 37, 462-476. [Google Scholar] [CrossRef] [PubMed]
[7] Palucka, A.K. and Coussens, L.M. (2016) The Basis of Oncoim-munology. Cell, 164, 1233-1247. [Google Scholar] [CrossRef] [PubMed]
[8] Kang, Y.K., Boku, N., Satoh, T., Ryu, M.H., Chao, Y., Kato, K., et al. (2017) Nivolumab in Patients with Advanced Gastric or Gastro-Oesophageal Junction Cancer Refractory to, or Intol-erant of, at Least Two Previous Chemotherapy Regimens (ONO-4538-12,ATTRACTION-2): A Randomised, Dou-ble-Blind, Placebo-Controlled, Phase 3 Trial. Lancet, 390, 2461-2471. [Google Scholar] [CrossRef] 
[9] Fuchs, C.S., Doi, T., Jang, R.W., Muro, K., Satoh, T., Ma-chado, M., et al. (2018) Safety and Efficacy of Pembrolizumab Mono Therapy in Patients with Previously Treated Ad-vanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncology, 4, Arti-cle ID: e180013.
[10] Wainberg, Z.A., Shitara, K., Van Cutsem, E., Wyrwicz, L., Lee, K.W., Kudaba, I., et al. (2022) Pembrolizumab with or without Chemotherapy versus Chemotherapy alone for Patients with PD-L1 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: Update from the Phase 3 KEYNOTE-062 Trial. Journal of Clin-ical Oncology, 40, 243. [Google Scholar] [CrossRef] 
[11] Janjigian, Y.Y., Shitara, K., Moehler, M., Garrido, M., Salman, P., Shen, L., et al. (2021) First-Line Nivolumab plus Chemotherapy versus Chemo-therapy alone for Advanced Gastric, Gastro-Oesophageal Junction, and Oesophageal Adenocarcinoma(CheckMate 649): A Randomised, Open-Label, Phase 3 Trial. Lancet, 398, 27-40. [Google Scholar] [CrossRef] 
[12] Shitara, K., Janjigian, Y.Y., Moehler, M.H., Garrido, M., Gallardo, C., Shen, L., et al. (2022) Nivolumab (NIVO) plus Chemotherapy (Chemo) versus Chemo as First-Line (1L) Treatment for Advanced Gastric Cancer/Gastroesophageal Junction Cancer/Esophageal Adenocarcinoma (GC/GEJC/EAC): Expanded Efficacy, Safety, and Subgroup Analyses from CheckMate 649. Journal of Clinical Oncol-ogy, 40, 240. [Google Scholar] [CrossRef] 
[13] Boku, N., Ryu, M.H., Oh, D.Y., Oh, S.C., Chung, H.C., Lee, K.-W., et al. (2020) LBA7_ PR Nivolumab plus Chemotherapy versus Chemotherapy alone in Pa-tients with Previously Untreated Advanced or Recurrent Gastric/Gastroeso- phageal Junction (G/GEJ) Cancer: ATTRACTION-4 (ONO-4538-37) Study. Annals of Oncology, 31, S1192. [Google Scholar] [CrossRef] 
[14] Xu, J., Jiang, H., Pan, Y., Gu, K., Cang, S., Han, L., et al. (2021) LBA53-Sintilimab plus Chemotherapy(Chemo) versus Chemo as First-Line Treatment for Advanced Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma (ORIENT-16): First Results of a Randomized, Double-Blind, Phase Ⅲ Study. Annals of Oncology, 32, S1331. [Google Scholar] [CrossRef] 
[15] Ji, J., Shen, L., Gao, X., Ji, K., Chen, Y., Xu, N., et al. (2022) A Phase Ib/II, Multicenter, Open-Label Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, Combined with Chemo-therapy (Chemo) as First-Line Therapy for Advanced Gastric (G) or Gastroesophageal Junction (GEJ) Cancer. Journal of Clinical Oncology, 40, 308. [Google Scholar] [CrossRef] 
[16] 潘云枫. HER2阳性胃癌免疫治疗的研究进展[J]. 中国肿瘤生物治疗杂志, 2021, 28(1): 90-96
[17] 程浩, 依荷芭丽•迟, 周全, 应建明, 石素胜. CAR-T在胃癌免疫治疗中的研究进展[J/OL]. 中国肿瘤临床.
https://kns.cnki.net/kcms/detail/12.1099.R.20220129.1559.006.html, 2022-01-30.
[18] 谢通, 沈琳. 2021年度胃癌治疗进展[J]. 肿瘤综合治疗电子杂志, 2022, 8(1): 56-60
[19] Qi, C., Qin, Y., Liu, D., Gong, J., Ge, S., Zhang, M., et al. (2021) 1372O CLDN 18.2-Targeted CAR-T Cell Therapy in Patients with Cancers of the Digestive System. Annals of Oncology, 32, S1040. [Google Scholar] [CrossRef] 
[20] Peng, Z., Liu, T., Wei, J., Wang, A., He, Y., Yang, L., et al. (2021) Efficacy and Safety of a Novel Anti-HER2 Therapeutic Antibody RC48 in Patients with HER2- Overexpressing, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer: A Single-Arm Phase II Study. Cancer Communications, 41, 1173-1182. [Google Scholar] [CrossRef] [PubMed]
[21] Shitara, K., Bang, Y.J., Iwasa, S., Sugimoto, N., Ryu, M.H., Sakai, D., et al. (2020) Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. The New England Journal of Medicine, 382, 2419-2430. [Google Scholar] [CrossRef] 
[22] Janjigian, Y.Y., Kawazoe, A., Yañez, P., Li, N., Lonardi, S., Kole-snik, O., et al. (2021) The KEYNOTE-811 Trial of Dual PD-1 and HER2 Blockade in HER2-Positive Gastric Cancer. Nature, 600, 727-730. [Google Scholar] [CrossRef] [PubMed]
[23] Zhang, J., Dong, R. and Shen, L. (2020) Evaluation and Reflec-tion on Claudin 18.2 Targeting Therapy in Advanced Gastric Cancer. Chinese Journal of Cancer Research, 32, 263-270. [Google Scholar] [CrossRef] [PubMed]
[24] Sahin, U., Koslowski, M., Dhaene, K., Usener, D., Brandenburg, G., Seitz, G., et al. (2008) Claudin-18 Splice Variant 2 Is a Pan-Cancer Target Suitable for Therapeutic Antibody Development. Clinical Cancer Research, 14, 7624-7634. [Google Scholar] [CrossRef] 
[25] Sahin, U., Türeci, Ö., Manikhas, G., Lordick, F., Rusyn, A., et al. (2021) FAST: A Randomised Phase II Study of Zolbetuximab (IMAB362) plus EOX versus EOX alone for First-Line Treatment of Advanced CLDN18.2-Positive Gastric and Gastro-Oesophageal Adenocarcinoma. Annals of Oncology, 32, 609-619. [Google Scholar] [CrossRef] [PubMed]

为你推荐