Esophageal adenocarcinoma (EAC) is a highly lethal malignancy. Due to its rising incidence, EAC has become a severe health challenge in Western countries. Current treatment strategies are mainly chosen based on disease stage and clinical features, whereas the biological background is hardly considered. In this study, we performed a comprehensive review of existing studies and discussed how etiology, genetics and epigenetic characteristics, together with the tumor microenvironment, contribute to the malignant behavior and dismal prognosis of EAC. During the development of EAC, several intestinal-type proteins and signaling cascades are induced. The anti-inflammatory and immunosuppressive microenvironment is associated with poor survival. The accumulation of somatic mutations at the early phase and chromosomal structural rearrangements at relatively later time points contribute to the dynamic and heterogeneous genetic landscape of EAC. EAC is also characterized by frequent DNA methylation and dysregulation of microRNAs. We summarize the findings of dysregulations of specific cytokines, chemokines and immune cells in the tumor microenvironment and conclude that DNA methylation and microRNAs vary with each different phase of BE, LGD, HGD, early EAC and invasive EAC. Furthermore, we discuss the suitability of the currently employed therapies in the clinic and possible new therapies in the future. The development of targeted and immune therapies has been hampered by the heterogeneous genetic characteristics of EAC. In view of this, the up-to-date knowledge revealed by this work is absolutely important for future EAC studies and the discovery of new therapeutics.
食管腺癌是一种高度致命的恶性肿瘤。由于其发病率不断上升，食管腺癌已成为西方国家面临的严峻健康挑战。目前的治疗策略主要基于疾病分期和临床特征进行选择，而生物学背景因素却很少被考虑。本研究对现有文献进行了全面综述，探讨了病因学、遗传与表观遗传特征以及肿瘤微环境如何共同影响食管腺癌的恶性行为和不良预后。在食管腺癌发展过程中，多种肠型蛋白和信号级联反应被激活。抗炎和免疫抑制微环境与患者生存率降低密切相关。早期体细胞突变的积累和相对晚期染色体结构重排共同构成了食管腺癌动态且异质性的遗传图谱。该疾病还具有DNA频繁甲基化和microRNA失调的特征。我们总结了肿瘤微环境中特定细胞因子、趋化因子和免疫细胞失调的研究发现，并指出DNA甲基化和microRNA在巴雷特食管、低级别上皮内瘤变、高级别上皮内瘤变、早期食管腺癌及浸润性食管腺癌各阶段呈现动态变化。此外，我们探讨了当前临床治疗方案的适用性及未来潜在的新疗法。由于食管腺癌异质性的遗传特征，靶向治疗和免疫疗法的研发进展受到制约。鉴于此，本研究揭示的最新认知对未来的食管腺癌研究和新型治疗方法的发现具有至关重要的意义。
Molecular Biology and Clinical Management of Esophageal Adenocarcinoma
肿瘤(癌症)患者之家