Dhakras Purabi, Uboha Nataliya, Horner Vanessa, Reinig Erica, Matkowskyj Kristina A
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA.
Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin, Madison, WI, USA.
Transl Gastroenterol Hepatol. 2020 Oct 5;5:55. doi: 10.21037/tgh.2020.01.08. eCollection 2020.
Esophageal and gastric adenocarcinomas are frequently diagnosed at an advanced stage and have a dismal prognosis. Even in patients with potentially curative cancer, nearly 50% will develop recurrent disease despite aggressive treatments. A number of biomarkers currently guide treatment decisions for patients with esophageal and gastric adenocarcinoma and include human epidermal growth factor receptor 2 (HER2) amplification, mismatch repair deficiency/microsatellite instability (dMMR/MSI-H) and program death-ligand 1 (PD-L1) expression. This review will focus on the function, testing and FDA-approved targeted therapies for HER2, dMMR/MSI-H and PD-L1. In addition, a number of novel targets in esophageal and gastric cancer are being studied in clinical trials. Neurotrophic-tropomyosin receptor kinase (NTRK), claudin-18 (CLDN18)/Rho GTPase activating protein 26 () gene fusion, fibroblast growth factor receptor (FGFR), lymphocyte-activation gene 3 (LAG3) and T cell immunoglobulin and mucin-domain containing-3 (TIM3) will be briefly reviewed. Despite several biomarkers used in the selection of treatment therapies, treatment outcomes remain poor. Future research efforts will focus on the identification of new biomarkers, moving existing biomarkers into earlier lines of therapy, and evaluating new combinations of existing biomarkers and therapies.
食管腺癌和胃腺癌常在晚期被诊断出来,预后不佳。即使是患有潜在可治愈癌症的患者,尽管接受了积极治疗,仍有近50%会出现疾病复发。目前,一些生物标志物可指导食管和胃腺癌患者的治疗决策,包括人表皮生长因子受体2(HER2)扩增、错配修复缺陷/微卫星高度不稳定(dMMR/MSI-H)以及程序性死亡配体1(PD-L1)表达。本综述将聚焦于HER2、dMMR/MSI-H和PD-L1的功能、检测方法以及美国食品药品监督管理局(FDA)批准的靶向治疗。此外,一些食管癌和胃癌的新靶点正在临床试验中进行研究。神经营养性原肌球蛋白受体激酶(NTRK)、紧密连接蛋白18(CLDN18)/Rho鸟苷三磷酸酶激活蛋白26()基因融合、成纤维细胞生长因子受体(FGFR)、淋巴细胞激活基因3(LAG3)以及含T细胞免疫球蛋白和粘蛋白结构域3(TIM3)将被简要综述。尽管在治疗方案选择中使用了多种生物标志物,但治疗效果仍然不佳。未来的研究工作将集中在识别新的生物标志物、将现有生物标志物应用于更早的治疗阶段,以及评估现有生物标志物和治疗方法的新组合。