Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Translational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan.
Nat Rev Clin Oncol. 2021 Aug;18(8):473-487. doi: 10.1038/s41571-021-00492-2. Epub 2021 Mar 31.
Advances in cancer biology and sequencing technology have enabled the selection of targeted and more effective treatments for individual patients with various types of solid tumour. However, only three molecular biomarkers have thus far been demonstrated to predict a response to targeted therapies in patients with gastric and/or gastro-oesophageal junction (G/GEJ) cancers: HER2 positivity for trastuzumab and trastuzumab deruxtecan, and microsatellite instability (MSI) status and PD-L1 expression for pembrolizumab. Despite this lack of clinically relevant biomarkers, distinct molecular subtypes of G/GEJ cancers have been identified and have informed the development of novel agents, including receptor tyrosine kinase inhibitors and monoclonal antibodies, several of which are currently being tested in ongoing trials. Many of these trials include biomarker stratification, and some include analysis of circulating tumour DNA (ctDNA), which both enables the noninvasive assessment of biomarker expression and provides an indication of the contributions of intratumoural heterogeneity to response and resistance. The results of these studies might help to optimize the selection of patients to receive targeted therapies, thus facilitating precision medicine approaches for patients with G/GEJ cancers. In this Review, we describe the current evidence supporting the use of targeted therapies in patients with G/GEJ cancers and provide guidance on future research directions.
癌症生物学和测序技术的进步使我们能够为各种实体瘤患者选择靶向和更有效的治疗方法。然而，到目前为止，只有三种分子生物标志物被证明可以预测胃癌和/或胃食管结合部（G/GEJ）癌症患者对靶向治疗的反应：曲妥珠单抗和 trastuzumab deruxtecan 治疗的 HER2 阳性，以及 pembrolizumab 治疗的微卫星不稳定性（MSI）状态和 PD-L1 表达。尽管缺乏具有临床意义的生物标志物，但已经确定了 G/GEJ 癌症的不同分子亚型，并为新型药物的开发提供了信息，包括受体酪氨酸激酶抑制剂和单克隆抗体，其中一些目前正在进行的试验中进行测试。这些试验中的许多都包括生物标志物分层，其中一些包括循环肿瘤 DNA（ctDNA）的分析，这既可以非侵入性地评估生物标志物的表达，也可以表明肿瘤内异质性对反应和耐药性的贡献。这些研究的结果可能有助于优化选择接受靶向治疗的患者，从而为 G/GEJ 癌症患者提供精准医学方法。在这篇综述中，我们描述了支持在 G/GEJ 癌症患者中使用靶向治疗的现有证据，并提供了未来研究方向的指导。
