Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63130, USA.
Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63130, USA.
J Mol Cell Biol. 2020 Aug 1;12(8):593-606. doi: 10.1093/jmcb/mjaa035.
Gastroesophageal cancers are leading causes of cancer death. Our attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and pathways. It is clear that we should no longer treat all gastroesophageal cancers as a homogeneous disease, which is what we do when we use non-specific chemotherapy. However, we currently cannot monitor successful gene/pathway targeting, nor understand how/when tumors develop resistance, nor predict which patients will derive maximal benefit. To improve outcomes, we must precisely detail the heterogeneity of these tumors to then individualize cancer therapy as well as develop novel avenues to study and predict treatment effects in individual patients. To this end, patient-derived organoids, in which tumor cells from individual patients are grown in a Petri dish, are a new versatile system that allows for timely expandability, detailed molecular characterization, and genetic manipulation with the promise of enabling predictive assessment of treatment response. In this review, we will explore the development and basic techniques for organoid generation, and discuss the current and potential future applications of this exciting technology to study the basic science of carcinogenesis and to predict/guide cancer patient care in the clinics.
胃食管癌症是癌症死亡的主要原因。尽管我们开始确定特定的可靶向基因突变和途径,但我们采用基于分子的治疗方法的尝试一直缓慢且无效。很明显,我们不应该再将所有胃食管癌症视为一种同质疾病,这就是我们在使用非特异性化疗时所做的。然而,我们目前无法监测成功的基因/途径靶向,也不了解肿瘤何时以及如何产生耐药性,也无法预测哪些患者将获得最大益处。为了改善结果,我们必须详细描述这些肿瘤的异质性,然后将癌症治疗个体化,并开发新的途径来研究和预测个体患者的治疗效果。为此,源自患者的类器官是一种新的多功能系统,其中来自单个患者的肿瘤细胞在培养皿中生长,可以进行及时的扩展性、详细的分子特征分析和遗传操作,并有望实现对治疗反应的预测评估。在这篇综述中,我们将探讨类器官生成的发展和基本技术,并讨论这项令人兴奋的技术在研究致癌发生的基础科学以及预测/指导临床癌症患者护理方面的当前和潜在未来应用。