Fontana Elisa, Smyth Elizabeth C
Royal Marsden Hospital, Sutton, UK.
Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, UK.
Ther Adv Med Oncol. 2016 Mar;8(2):113-25. doi: 10.1177/1758834015616935.
Gastric cancer is responsible for a high burden of disease globally. Although more extensive use of chemotherapy together with the recent introduction of the two targeted agents trastuzumab and ramucirumab have contributed to marginal outcome prolongation, overall survival for patients with advanced stage disease remains poor. Over the last decade, a number of novel agents have been examined in clinical trials with largely disappointing results. Potential explanations for this are the absence of molecularly selected trial populations or weak predictive biomarkers within the context of a highly heterogeneous disease. In the recently published gastric cancer The Cancer Genome Atlas (TCGA) project a new classification of four different tumour subtypes according to different molecular characteristics has been proposed. With some overlap, several relatively distinct and potentially targetable pathways have been identified for each subtype. In this perspective review we match recent trial results with the subtypes described in the gastric cancer TCGA aiming to highlight data regarding novel agents under evaluation and to discuss whether this publication might provide a framework for future drug development.
胃癌在全球范围内造成了沉重的疾病负担。尽管化疗的更广泛应用以及最近两种靶向药物曲妥珠单抗和雷莫西尤单抗的引入,在一定程度上延长了患者的生存期,但晚期胃癌患者的总体生存率仍然很低。在过去十年中,许多新型药物在临床试验中接受了检验,结果大多令人失望。造成这种情况的潜在原因是,在这种高度异质性疾病的背景下,缺乏分子选择的试验人群或有效的预测生物标志物。在最近发表的胃癌癌症基因组图谱(TCGA)项目中,根据不同的分子特征,提出了四种不同肿瘤亚型的新分类。各亚型之间存在一些重叠,但已确定了几条相对独特且可能成为靶点的途径。在这篇观点综述中,我们将近期的试验结果与胃癌TCGA中描述的亚型进行匹配,旨在突出正在评估的新型药物的数据,并讨论该出版物是否可能为未来的药物开发提供一个框架。