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Current treatment and recent progress in gastric cancer. ​

文献信息 ​

DOI10.3322/caac.21657
PMID33592120
期刊CA: a cancer journal for clinicians
影响因子232.4
JCR 分区Q1
发表年份2021
被引次数911
关键词腺癌，胃癌，免疫治疗，分子亚型，胃肿瘤
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN0007-9235
页码264-279
期号71(3)
作者Smita S Joshi, Brian D Badgwell

一句话小结 ​

尽管在美国胃癌并非十大恶性肿瘤，但其在全球癌症死亡中占据重要地位，因不同地区的生物学差异使得标准治疗方案复杂。研究发现，基于分子亚型的个性化治疗及生物标志物的应用，尤其是微卫星不稳定性和PD-L1等，能有效推动胃腺癌的多学科治疗，识别出可能从免疫及靶向治疗中获益的患者群体。

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腺癌，胃癌，免疫治疗，分子亚型，胃肿瘤

摘要 ​

胃癌在美国并不是十大恶性肿瘤之一，但却是全球癌症死亡的主要原因之一。来自东部和西部国家肿瘤之间的生物学差异使得根据国际临床试验确定标准治疗方案的复杂性增加。系统性化疗、放疗、手术、免疫治疗和靶向治疗在胃腺癌中均已显示出有效性，因此多学科治疗在治疗选择中至关重要。对于可切除的胃癌，三联化疗目前已被接受，并可能代表局部疾病标准细胞毒性化疗的一个平台。基于分子亚型的胃癌分类为个性化治疗提供了机会。生物标志物，特别是微卫星不稳定性（MSI）、程序性细胞死亡配体1（PD-L1）、人类表皮生长因子受体2（HER2）、肿瘤突变负荷和埃普斯坦-巴尔病毒，正日益推动系统治疗方法，并使得能够识别出最有可能从免疫治疗和靶向治疗中受益的群体。对分化程度较低的胃腺癌组织学亚型以及那些没有免疫治疗活性标志物的病例，仍然存在重要的研究机会。

英文摘要 ​

Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard-of-care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein-Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.

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主要研究问题 ​

  1. 在胃癌的治疗中，如何评估不同分子亚型对治疗反应的影响？
  2. 免疫疗法在不同地区胃癌患者中的疗效是否存在显著差异？
  3. 近年来，靶向治疗在胃癌治疗中的具体应用有哪些成功案例？
  4. 如何优化多学科团队在胃癌治疗中的协作，以提高患者的整体生存率？
  5. 对于没有免疫治疗标志物的胃腺癌亚型，目前有哪些新兴的研究方向或治疗策略？

核心洞察 ​

研究背景和目的 ​

胃癌在美国并不属于十大恶性肿瘤，但却是全球癌症死亡的主要原因之一。由于东西方肿瘤之间的生物学差异，基于国际试验确定标准治疗方案的复杂性增加。本研究旨在探讨胃癌的多学科治疗选择，强调个体化治疗的潜力，尤其是在分子亚型分类和生物标志物的指导下。

主要方法/材料/实验设计 ​

本研究采用多学科治疗方法，结合系统性化疗、放疗、手术、免疫治疗和靶向治疗。以下是研究的技术路线图：

Mermaid diagram
  1. 胃癌诊断：通过影像学和内镜检查确诊胃癌。
  2. 分子亚型分类：根据分子特征对胃癌进行分类，以识别不同亚型。
  3. 生物标志物检测：检测MSI、PD-L1、HER2、肿瘤突变负荷和EB病毒等生物标志物。
  4. 个体化治疗方案选择：根据生物标志物结果选择最合适的治疗方案。
  5. 多学科治疗实施：整合化疗、放疗、手术和免疫治疗等多种治疗方式。
  6. 疗效评估：通过随访和影像学检查评估治疗效果。

关键结果和发现 ​

  • 三联化疗已被接受为可切除胃癌的标准治疗，可能代表局部疾病化疗的一个高峰。
  • 生物标志物的检测正在推动系统性治疗的方法，特别是对于MSI、PD-L1、HER2等标志物阳性的患者。
  • 研究发现，某些低分化组织学亚型的胃腺癌及缺乏免疫治疗活性标志物的病例仍存在显著的研究机会。

主要结论/意义/创新性 ​

本研究强调了个体化治疗在胃癌管理中的重要性，特别是通过分子亚型和生物标志物的应用，可以优化治疗选择，提高患者的生存率和生活质量。创新性体现在推动了胃癌的精准医疗，尤其是在多学科合作的框架下，结合传统与新兴治疗方法。

研究局限性和未来方向 ​

  • 局限性：研究主要集中在生物标志物阳性患者的疗效，缺乏对低分化亚型的深入研究。
  • 未来方向：应加强对缺乏免疫治疗标志物的胃癌亚型的研究，探索新的治疗靶点和策略。同时，扩大临床试验的规模，以验证个体化治疗方案的有效性。
研究要素内容摘要
研究背景胃癌是全球癌症死亡的重要原因
主要方法多学科治疗，结合生物标志物和化疗
关键结果三联化疗为标准治疗，个体化治疗潜力
主要结论精准医疗可提高患者生存率和生活质量
研究局限性对低分化亚型研究不足
未来方向加强对缺乏标志物亚型的研究

参考文献 ​

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  2. Circulating Tumor DNA Sequencing Analysis of Gastroesophageal Adenocarcinoma. - Steven B Maron;Leah M Chase;Samantha Lomnicki;Sara Kochanny;Kelly L Moore;Smita S Joshi;Stacie Landron;Julie Johnson;Lesli A Kiedrowski;Rebecca J Nagy;Richard B Lanman;Seung Tae Kim;Jeeyun Lee;Daniel V T Catenacci - Clinical cancer research : an official journal of the American Association for Cancer Research (2019)
  3. Preoperative accuracy of gastric cancer staging in patient selection for preoperative therapy: race may affect accuracy of endoscopic ultrasonography. - Naruhiko Ikoma;Jeffrey H Lee;Manoop S Bhutani;William A Ross;Brian Weston;Yi-Ju Chiang;Mariela A Blum;Tara Sagebiel;Catherine E Devine;Aurelio Matamoros;Keith Fournier;Paul Mansfield;Jaffer A Ajani;Brian D Badgwell - Journal of gastrointestinal oncology (2017)
  4. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. - J A Ajani;P F Mansfield;N Janjan;J Morris;P W Pisters;P M Lynch;B Feig;R Myerson;R Nivers;D S Cohen;L L Gunderson - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2004)
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引用本文的文献 ​

  1. Everything, in Retrospect, is Obvious. - Brian Badgwell - Annals of surgical oncology (2021)
  2. The emerging role of miR-10 family in gastric cancer. - Fang Liu;Yanfen Shi;Zuolong Liu;Ziyi Li;Wei Xu - Cell cycle (Georgetown, Tex.) (2021)
  3. The RNA-Binding Protein NELFE Promotes Gastric Cancer Growth and Metastasis Through E2F2. - Changyu Chen;Qiang Zheng;Shubo Pan;Wenzheng Chen;Jianfeng Huang;Yi Cao;Yi Tu;Zhengrong Li;Changjun Yu;Zhigang Jie - Frontiers in oncology (2021)
  4. Prognostic Role of Receptor Tyrosine Kinase-Like Orphan Receptors in Intestinal-Type Gastric Cancer. - Rajeev Nema;Priti Patel;Ashok Kumar - Asian Pacific journal of cancer prevention : APJCP (2021)
  5. Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors. - Donghui Liu;Xuyao Wang;Enhong Shi;Liru Wang;Minghao Nie;Long Li;Qingxin Jiang;Pengyu Kong;Shuai Shi;Chao Wang;Sen Yan;Zhihui Qin;Shuang Zhao - Frontiers in genetics (2021)
  6. Effect of LAMA4 on Prognosis and Its Correlation with Immune Infiltration in Gastric Cancer. - Mingming Wang;Changzheng Li;Ying Liu;Zuomin Wang - BioMed research international (2021)
  7. Safety and Efficacy of Laparoscopic Versus Open Gastrectomy in Patients With Advanced Gastric Cancer Following Neoadjuvant Chemotherapy: A Meta-Analysis. - Xu-Liang Liao;Xian-Wen Liang;Hua-Yang Pang;Kun Yang;Xin-Zu Chen;Xiao-Long Chen;Kai Liu;Lin-Yong Zhao;Wei-Han Zhang;Jian-Kun Hu - Frontiers in oncology (2021)
  8. LncRNA PITPNA-AS1 promotes gastric cancer by increasing SOX4 expression via inhibition of miR-92a-3p. - Licheng Liu;Anna Dai;Zao Zhang;Meiying Ning;Dong Han;Li Li;Zhuangzhuang Li - Aging (2021)
  9. Efficiency of complete omentectomy in patients with resectable gastric cancer: a meta‑analysis and systematic review. - Akao Zhu;Guang Yin;Xinchun Liu;Wencheng Kong;Yu Zhang;Yuqiang Shan;Rongchao Ying;Jian Zhang;Chunhua Zhou - BMC gastroenterology (2021)
  10. Tumor-Infiltrating Neutrophils and Non-Classical Monocytes May Be Potential Therapeutic Targets for HER2negative Gastric Cancer. - Juhee Jeong;Duk Ki Kim;Ji-Hyeon Park;Do Joong Park;Hyuk-Joon Lee;Han-Kwang Yang;Seong-Ho Kong;Keehoon Jung - Immune network (2021)

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