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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 ​

胃癌在全球范围内是主要的癌症死亡原因，尽管在美国并不常见，治疗方法包括化疗、放疗、手术、免疫疗法和靶向治疗等多学科策略显示出有效性。研究表明，基于分子亚型的分类和生物标志物的应用为个性化治疗提供了机会，尤其是在针对可切除的胃癌和低分化腺癌的治疗上，仍然存在重要的研究潜力。

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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，但在全球范围内却是癌症死亡的主要原因之一。来自东部和西部国家的肿瘤之间的生物学差异增加了基于国际试验确定标准治疗的复杂性。全身化疗、放疗、手术、免疫疗法和靶向治疗在胃腺癌中均已证明有效，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，三联化疗现在已被认可，并可能代表局部疾病的标准细胞毒性化疗的一个高峰。基于分子亚型对胃癌的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）、人表皮生长因子受体2（HER2）、肿瘤突变负荷和埃博拉病毒，越来越多地推动全身治疗方法，并允许识别最可能从免疫疗法和靶向治疗中获益的人群。对于分化程度较低的胃腺癌组织学亚型以及那些没有免疫疗法活性标志物的病例，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. 如何评估不同国家之间胃癌治疗方案的有效性差异？
  2. 在个性化治疗中，如何利用分子亚型分类来优化胃癌患者的治疗选择？
  3. 目前有哪些新的生物标志物正在研究中，可能会影响胃癌的治疗策略？
  4. 对于未分化的胃腺癌亚型，未来的研究方向和治疗进展有哪些？
  5. 免疫治疗在胃癌中的应用前景如何，尤其是在缺乏免疫治疗活性标志物的患者中？

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，但在全球范围内却是癌症死亡的主要原因之一。由于东西方肿瘤之间存在生物学差异，基于国际试验确定标准治疗方案的复杂性加大。本研究旨在探讨胃腺癌的多学科治疗选择，尤其是在个体化治疗和生物标志物驱动的系统治疗方面的最新进展。

主要方法/材料/实验设计 ​

本研究采用文献回顾和分析的方法，综合评估当前胃腺癌的治疗方案及其生物标志物的应用。重点分析以下治疗方法：

  • 系统化疗：探讨三联化疗在可切除胃癌中的应用。
  • 分子分型：分析基于分子亚型的个体化治疗机会。
  • 生物标志物：评估微卫星不稳定性（MSI）、程序性死亡配体1（PD-L1）、人类表皮生长因子受体2（HER2）、肿瘤突变负荷和EB病毒等标志物对治疗选择的影响。

以下是研究的技术路线图：

Mermaid diagram

关键结果和发现 ​

  1. 三联化疗：已被广泛接受为可切除胃癌的标准化疗方案，显示出良好的疗效。
  2. 分子分型：为个体化治疗提供了新的机会，通过识别不同分子亚型患者的治疗反应。
  3. 生物标志物：MSI、PD-L1和HER2等生物标志物在系统治疗中发挥越来越重要的作用，能够帮助识别最可能从免疫治疗和靶向治疗中获益的患者。

主要结论/意义/创新性 ​

本研究强调了胃腺癌治疗的多学科方法及其个体化的重要性。随着对生物标志物的深入研究，未来的治疗方案将更加精准，能够根据患者的具体生物学特征进行定制，从而提高治疗效果。此研究为胃癌的未来治疗方向提供了新的视角，尤其是在生物标志物驱动的个体化治疗方面。

研究局限性和未来方向 ​

  1. 局限性：当前研究主要基于文献综述，缺乏大规模临床试验数据的支持，可能影响结果的普遍适用性。
  2. 未来方向：
    • 深入研究胃腺癌中分化不良组织学亚型的治疗方案。
    • 探索新的生物标志物及其在免疫治疗中的潜在应用。
    • 进行多中心、前瞻性的临床试验，以验证不同治疗方案的有效性和安全性。

通过上述研究，胃癌的治疗方法和生物标志物的应用将有助于提升患者的生存率和生活质量。

参考文献 ​

  1. Race Is a Risk for Lymph Node Metastasis in Patients With Gastric Cancer. - Naruhiko Ikoma;Mariela Blum;Yi-Ju Chiang;Jeannelyn S Estrella;Sinchita Roy-Chowdhuri;Keith Fournier;Paul Mansfield;Jaffer Ajani;Brian D Badgwell - Annals of surgical oncology (2017)
  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)
  5. It Is Time to Stop Using Epirubicin to Treat Any Patient With Gastroesophageal Adenocarcinoma. - Elena Elimova;Yelena Y Janjigian;Mary Mulcahy;Daniel V Catenacci;Mariela A Blum;Khaldoun Almhanna;J Randolph Hecht;Jaffer A Ajani - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2017)
  6. GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study. - Olivier Glehen;Guillaume Passot;Laurent Villeneuve;Delphine Vaudoyer;Sylvie Bin-Dorel;Gilles Boschetti;Eric Piaton;Alfredo Garofalo - BMC cancer (2014)
  7. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. - Yung-Jue Bang;Eric Van Cutsem;Andrea Feyereislova;Hyun C Chung;Lin Shen;Akira Sawaki;Florian Lordick;Atsushi Ohtsu;Yasushi Omuro;Taroh Satoh;Giuseppe Aprile;Evgeny Kulikov;Julie Hill;Michaela Lehle;Josef Rüschoff;Yoon-Koo Kang; - Lancet (London, England) (2010)
  8. Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial. - J Randolph Hecht;Yung-Jue Bang;Shukui K Qin;Hyun C Chung;Jianming M Xu;Joon O Park;Krzysztof Jeziorski;Yaroslav Shparyk;Paulo M Hoff;Alberto Sobrero;Pamela Salman;Jin Li;Svetlana A Protsenko;Zev A Wainberg;Marc Buyse;Karen Afenjar;Vincent Houé;Agathe Garcia;Tomomi Kaneko;Yingjie Huang;Saba Khan-Wasti;Sergio Santillana;Michael F Press;Dennis Slamon - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2016)
  9. Low metabolic activity in primary gastric adenocarcinoma is associated with resistance to chemoradiation and the presence of signet ring cells. - Kazuto Harada;Madhavi Patnana;Xuemei Wang;Masaaki Iwatsuki;Mariela A Blum Murphy;Meina Zhao;Prajnan Das;Bruce D Minsky;Brian Weston;Jeffrey H Lee;Manoop S Bhutani;Jeannelyn S Estrella;Namita Shanbhag;Naruhiko Ikoma;Brian D Badgwell;Jaffer A Ajani - Surgery today (2020)
  10. Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer: Post Hoc Analysis of the CLASSIC Randomized Controlled study. - Yoon Young Choi;Hyunki Kim;Su-Jin Shin;Ha Yan Kim;Jinae Lee;Han-Kwang Yang;Woo Ho Kim;Young-Woo Kim;Myeong-Cherl Kook;Young Kyu Park;Hyung-Ho Kim;Hye Seung Lee;Kyung Hee Lee;Mi Jin Gu;Seung Ho Choi;SoonWon Hong;Jong Won Kim;Woo Jin Hyung;Sung Hoon Noh;Jae-Ho Cheong - Annals of surgery (2019)

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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