EBV相关性胃癌分子特征及可能的治疗策略

Molecular characterizations and possible treatment strategies for Epstein-Barr virus-associated gastric cancer

2014年癌症基因组图谱(TCGA)将胃癌在分子水平分为四型:EB病毒感染型、基因组稳定型、染色体不稳定型及微卫星不稳定型。其中EBV相关性胃癌(Epstein-Barr virus-associated gastric cancer,EBVaGC)因具有PD-L1/2扩增/过表达的分子特性,有望成为免疫治疗的适宜群体而受到关注。了解EBVaGC的分子特征对胃癌机制研究及指导治疗有重要意义。目前,EBVaGC分子特征包括PD-L1/2过表达、PIK3CA突变、ARID1A突变、DNA超甲基化及TP53低突变等;相应地,可能的治疗策略有靶向免疫检查点抑制剂、靶向PI3K/AKT通路抑制剂及抗病毒治疗等。本文就上述EBVaGC的重要分子特征及可能的治疗策略进行综述。

In 2014, The Cancer Genome Atlas （TCGA） classified gastric cancer into four types based on the genotype include EBV-infect- ed tumors, genomically stable tumors, chromosomally unstable tumors and MSI tumors, among which Epstein-Barr virus-associated gastric cancer （EBVaGC） is expected to be most suitable for immunotherapy because of its molecular characteristics, such as PD-L1/2 amplification or upregulation. Understanding the molecular characterizations of EBVaGC is very important in clinical practice. The reported molecular characteristics of EBVaGC include： PD-L1/2 upregulation, PIK3CA mutation, ARID1A mutation, DNA hypermethylation, and rare mutation of TP53. Therefore, the possible therapeutic strategies for EBVaGC include the use of immune checkpoint inhibitors, PI3K/AKT signaling pathway inhibitors, or antiviral therapy. This review summarizes the important molecular characterizations and possible treatment strategies for EBVaGC.