Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Shibakoen, Minato-ku, Tokyo, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
J Gastroenterol Hepatol. 2019 Nov;34(11):1906-1910. doi: 10.1111/jgh.14773. Epub 2019 Jul 31.
Biliary tract cancers and pancreatic cancers are aggressive malignancies that are difficult to diagnose early and have a poor prognosis. Patients with inoperable biliary tract and pancreatic cancers generally receive chemotherapy regimens including gemcitabine. However, the effects of these drugs are limited, and the 5-year survival rates of patients are very low. The newly developed three-dimensional culture system known as "organoid culture" allows long-term expansion of stem cells into cyst-like structures (organoids) with properties resembling those of the original tissues. We and other groups have successfully established long-term in vitro cultures of organoids derived from biliary tract and pancreatic cancers. Organoids derived from biliary tract and pancreatic cancers closely recapitulate the properties of the original tumors including genetic alterations, gene expression profiles, and histopathological structures. These patient-derived cancer organoids can be applied for drug sensitivity testing, drug screening, epigenetic therapy, and differentiation-inducing therapy to identify therapeutic agents optimal for each patient. We intend to further establish organoids derived from various cancer cases and construct an organoid bank of biliary tract and pancreatic cancers. These powerful in vitro preclinical models of refractory cancers may bridge the gap between basic research and clinical trials and allow personalized therapy for patients.
胆道癌和胰腺癌是侵袭性恶性肿瘤,早期诊断困难,预后不良。不可手术的胆道和胰腺癌患者通常接受包括吉西他滨在内的化疗方案。然而,这些药物的疗效有限,患者的 5 年生存率非常低。新开发的三维培养系统,称为“类器官培养”,允许干细胞长期扩增成具有类似于原始组织特性的囊状结构(类器官)。我们和其他小组已经成功地建立了胆道和胰腺癌来源的类器官的长期体外培养。胆道和胰腺癌来源的类器官紧密重现了原始肿瘤的特性,包括遗传改变、基因表达谱和组织病理学结构。这些源自患者的癌症类器官可用于药物敏感性测试、药物筛选、表观遗传治疗和诱导分化治疗,以确定对每个患者最佳的治疗药物。我们打算进一步建立各种癌症病例的类器官,并构建胆道和胰腺癌的类器官库。这些针对难治性癌症的强大体外临床前模型可能会缩小基础研究和临床试验之间的差距,并为患者提供个性化治疗。