胃癌与基因组学:文献综述。

Gastric cancer and genomics: review of literature.

机构信息

Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, Tottori, 683-8504, Japan.

出版信息

J Gastroenterol. 2022 Aug;57(8):505-516. doi: 10.1007/s00535-022-01879-3. Epub 2022 Jun 25.

Abstract

Gastric cancer (GC) is a major health concern in many countries. GC is a heterogeneous disease stratified by histopathological differences. However, these variations are not used to determine GC management. Next-generation sequencing (NGS) technologies have become widely used, and cancer genomic analysis has recently revealed the relationships between various malignant tumors and genomic information. In 2014, studies using whole-exome sequencing (WES) and whole-genome sequencing (WGS) for GC revealed the entire structure of GC genomics. Genomics with NGS has been used to identify new therapeutic targets for GC. Moreover, personalized medicine to provide specific therapy for targets based on multiplex gene panel testing of tumor tissues has become of clinical use. Recently, immune checkpoint inhibitors (ICIs) have been used for GC treatment; however, their response rates are limited. To predict the anti-tumor effects of ICIs for GC and to select patients suitable for ICI treatment, genomics also provides informative data not only of tumors but also of tumor microenvironments, such as tumor-infiltrating lymphocytes. In therapeutic strategies for unresectable or recurrent malignant tumors, the target is not only the primary lesion but also metastatic lesions, and metastatic lesions are often resistant to chemotherapy. Unlike colorectal carcinoma, there is a heterogeneous status of genetic variants between the primary and metastatic lesions in GC. Liquid biopsy analysis is also helpful for predicting the genomic status of both primary and metastatic lesions. Genomics has become an indispensable tool for GC treatment and is expected to be further developed in the future.

摘要

胃癌(GC)是许多国家的主要健康关注点。GC 是一种具有组织病理学差异的异质性疾病。然而,这些变化并未用于确定 GC 的管理方法。下一代测序(NGS)技术已得到广泛应用,癌症基因组分析最近揭示了各种恶性肿瘤与基因组信息之间的关系。2014 年,使用全外显子组测序(WES)和全基因组测序(WGS)进行 GC 的研究揭示了 GC 基因组学的全貌。NGS 基因组学已被用于确定 GC 的新治疗靶点。此外,基于肿瘤组织的多重基因panel 检测为靶向提供特定治疗的个性化医学已开始临床应用。最近,免疫检查点抑制剂(ICI)已被用于 GC 的治疗;然而,其应答率有限。为了预测 ICI 对 GC 的抗肿瘤作用,并选择适合 ICI 治疗的患者,基因组学不仅为肿瘤,也为肿瘤微环境(如肿瘤浸润淋巴细胞)提供了有意义的信息数据。在不可切除或复发性恶性肿瘤的治疗策略中,目标不仅是原发性病变,还有转移性病变,而转移性病变通常对化疗有耐药性。与结直肠癌不同,GC 中原发性和转移性病变之间存在遗传变异的异质性状态。液体活检分析也有助于预测原发性和转移性病变的基因组状态。基因组学已成为 GC 治疗不可或缺的工具,预计未来还将进一步发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d207/9308599/233896c4652d/535_2022_1879_Fig1_HTML.jpg

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