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Received:October 13, 2022 Published Online:July 19, 2023
Received:October 13, 2022 Published Online:July 19, 2023
中文摘要: 胃癌是人类第五大常见的恶性肿瘤,是癌症相关死亡的第三大主要原因。根据肿瘤分期,围手术期化疗支持的内镜或手术切除是患者唯一的治疗选择。由于缺少可靠的生物标志物且早期缺乏特异性的临床表现,胃癌的早期检测具有挑战性,总体存活率仍然很差。传统上,在体外和动物模型中使用癌细胞系研究胃肠道中肿瘤起始和进展的机制,但体外细胞培养的方法与大量的异常基因组突变体相关联,导致这些异常基因组变体就其(转移性)行为或对治疗的反应而言不再准确反映肿瘤的原始状态。而类器官是在三维培养的细胞聚集体,其生长特性与其原始组织相似。由于类器官是由新鲜的活检组织进行培养,保留了原始组织的遗传表型和行为特征方式,具有无限的自我更新和增殖能力。患者来源的类器官(PDO)库起着活的生物库的作用,可以对组织的特定功能、发育和疾病进行深入分析。胃癌PDO的成功建立为多种临床转化应用开辟了新前景。本文概述类器官发展进程、胃类器官的建立及类器官在胃癌中的应用,探讨当前类器官模型应用的局限性及可能的改进方法,以期在未来的基础研究和转化研究中,尤其在药物发现和个性化医学领域中实现最大获益。
Abstract:Gastric cancer ranks as the fifth most common human malignancy and the third leading cause of cancer related deaths. Depending on tumor stage, endoscopic or surgical resection supported by perioperative chemotherapy is the only curative option for patients. Due to lack of reliable biomarkers and specific early clinical manifestations, the early detection of gastric cancer is challenging, so the overall survival rate remains poor. Traditionally, the mechanisms of tumor initiation and progression in the gastrointestinal tract were studied using cancer cell lines in vitro and animal models, but the abnormal genomic variants could not accurately reflect the original state of tumor cells in terms of their metastatic characteristics or response to treatment because of method of in vitro cell culture being associated with a large number of abnormal genomic variants. However, organoids are cell aggregates cultured in three-dimensions, and their growth characteristics are similar to the original tissues. Being cultured from fresh biopsy tissue, the organoids retain the genetic phenotype and behavioral characteristics of the original tissue and have unlimited self-renewal and proliferation ability. The patient-derived organoid(PDO) serves as a living biobank for an in-depth analysis of tissue-specific functions, development and diseases. The successful establishment of gastric cancer PDOs opens up new perspectives for various clinical transformation applications. This paper summarizes the development process of organoids, the establishment of gastric organoids and its application in gastric cancer, to discuss the limitations of the current organoid model application and possible improvement methods, in order to maximize the benefits in the fulture basic research and translational research, especially in the field of drug discovery and personalized medicine.
keywords: Gastric cancer Organoids Three-dimensional culture system Drug screening Personalized treatment
文章编号: 中图分类号:R735.2 R318.1 文献标志码:A
基金项目:内蒙古自治区“草原英才”工程青年创新创业人才二层次(2020-44);内蒙古自治区自然科学基金项目(2021MS08021);教育部春晖计划项目(20180056)
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