Busslinger Georg A, Lissendorp Fianne, Franken Ingrid A, van Hillegersberg Richard, Ruurda Jelle P, Clevers Hans, de Maat Michiel F G
Royal Netherlands Academy of Arts and Sciences, Oncode Institute and Hubrecht Institute, 3584CT Utrecht, The Netherlands.
Department of Surgery, University Medical Center Utrecht, PO Box 85500, 3508GA Utrecht, The Netherlands.
Open Biol. 2020 Apr;10(4):190274. doi: 10.1098/rsob.190274. Epub 2020 Apr 8.
The incidence of adenocarcinoma at the gastrooesophageal junction increased over the last years. Curative treatment for patients with upper gastrointestinal (UGI) malignancies, such as oesophageal and gastric tumours, is challenging and requires a multidisciplinary approach. Radical surgical resection with complete lymphadenectomy is the cornerstone of UGI cancer treatment. Combined with peri-operative treatment (i.e. by applying CROSS, EOX or FLOT regimen), the survival is even better than with surgery alone. However, peri-operative treatment is not effective in all patients, and the most effective strategy is a topic of active debate, as is reflected by varying treatment guidelines between countries. UGI cancers are (epi)genetically highly heterogeneous. It is thus not likely that a uniform treatment will benefit all patients equally well. Over recent years, patient-derived organoids (PDOs) gained more and more interest as an prediction model that may assist as a diagnostic tool in the future to select and eventually optimize the best peri-operative treatments for each patient. PDOs can be derived from endoscopic tumour biopsies, which maintain heterogeneity in culture. They can be rapidly established and expanded in a relatively short time for drug screening experiments. This review summarizes the clinical and molecular aspects of oesophageal and gastric tumours, as well as the current progress and remaining challenges in the use of PDOs for drug and radiation screens.
近年来，胃食管交界腺癌的发病率有所上升。上消化道（UGI）恶性肿瘤（如食管和胃肿瘤）患者的根治性治疗具有挑战性，需要多学科方法。根治性手术切除并完整清扫淋巴结是UGI癌症治疗的基石。结合围手术期治疗（即采用CROSS、EOX或FLOT方案），生存率甚至比单纯手术更好。然而，围手术期治疗并非对所有患者都有效，最有效的策略仍是一个活跃的辩论话题，各国不同的治疗指南就反映了这一点。UGI癌症在（表观）遗传学上高度异质性。因此，统一的治疗方案不太可能使所有患者都同样受益。近年来，患者来源的类器官（PDO）作为一种预测模型越来越受到关注，未来它可能作为一种诊断工具，帮助为每位患者选择并最终优化最佳的围手术期治疗方案。PDO可以从内镜肿瘤活检中获得，活检样本在培养中保持异质性。它们可以在相对较短的时间内快速建立并扩增用于药物筛选实验。本综述总结了食管和胃肿瘤的临床和分子方面，以及在使用PDO进行药物和放射治疗筛选方面的当前进展和 remaining challenges。（原文中“remaining challenges”未翻译，可能是存在笔误，推测应为“剩余挑战”，但按照要求不添加解释说明，所以保留原文）
