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精准医学时代的胃癌曙光。

Dawn of precision medicine on gastric cancer.

机构信息

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.

出版信息

Int J Clin Oncol. 2019 Jul;24(7):779-788. doi: 10.1007/s10147-019-01441-x. Epub 2019 Apr 11.

Abstract

BACKGROUND

In recent years, a better understanding of tumor biology and molecular features of gastric cancer has been reached. It may serve as a roadmap for patient stratification and trials of targeted therapies. The apparent efficacy of PD-1 blockade might be limited to a relatively small subset of advanced gastric cancer patients.

MATERIALS AND METHODS

In this study, preclinical and clinical studies, which investigated molecular features, promising treatment targets, and immune checkpoint inhibitor in gastric cancer, were reviewed via PubMed and the congress webpages of the American Society of Clinical Oncology and European Society of Medical Oncology.

RESULTS

Next-generation sequencing technologies have defined the genomic landscape of gastric cancer. Indeed, several molecular classifications have been proposed, and distinct molecular subtypes have been identified. Based on these molecular profiles, clinical trials of new agents such as receptor tyrosine kinases inhibitors, antibody-drug conjugates, and IMAB362 (anti-Claudin 18.2) are ongoing. In addition, biomarkers to predict response during immune checkpoint inhibitors and combination therapy have been enthusiastically investigated.

CONCLUSION

Remarkable advances in an understanding of molecular profiles of gastric cancer enable the development of novel agents. The better treatment selection of immune checkpoint inhibitors or combination therapy should be established. These developments could facilitate precision medicine on gastric cancer in the near future.

摘要

背景

近年来,人们对胃癌的肿瘤生物学和分子特征有了更好的了解。这可能为患者分层和靶向治疗试验提供了一个路线图。PD-1 阻断的明显疗效可能仅限于一小部分晚期胃癌患者。

材料和方法

本研究通过 PubMed 和美国临床肿瘤学会和欧洲肿瘤内科学会的会议网页,回顾了研究胃癌分子特征、有前途的治疗靶点和免疫检查点抑制剂的临床前和临床研究。

结果

下一代测序技术定义了胃癌的基因组图谱。事实上,已经提出了几种分子分类,并确定了不同的分子亚型。基于这些分子特征,正在进行针对受体酪氨酸激酶抑制剂、抗体药物偶联物和 IMAB362(抗 Claudin 18.2)等新型药物的临床试验。此外,还积极研究了预测免疫检查点抑制剂和联合治疗反应的生物标志物。

结论

对胃癌分子特征的理解取得了显著进展,从而开发了新的药物。应该建立免疫检查点抑制剂或联合治疗的更好治疗选择。这些发展可能会在不久的将来促进胃癌的精准医学。

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