Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
InnoSer Belgium NV, 3590 Diepenbeek, Belgium.
Int J Mol Sci. 2022 Mar 15;23(6):3147. doi: 10.3390/ijms23063147.
Cancers affecting the gastrointestinal system are highly prevalent and their incidence is still increasing. Among them, gastric and pancreatic cancers have a dismal prognosis (survival of 5-20%) and are defined as difficult-to-treat cancers. This reflects the urge for novel therapeutic targets and aims for personalised therapies. As a prerequisite for identifying targets and test therapeutic interventions, the development of well-established, translational and reliable preclinical research models is instrumental. This review discusses the development, advantages and limitations of both patient-derived organoids (PDO) and patient-derived xenografts (PDX) for gastric and pancreatic ductal adenocarcinoma (PDAC). First and next generation multicellular PDO/PDX models are believed to faithfully generate a patient-specific avatar in a preclinical setting, opening novel therapeutic directions for these difficult-to-treat cancers. Excitingly, future opportunities such as PDO co-cultures with immune or stromal cells, organoid-on-a-chip models and humanised PDXs are the basis of a completely new area, offering close-to-human models. These tools can be exploited to understand cancer heterogeneity, which is indispensable to pave the way towards more tumour-specific therapies and, with that, better survival for patients.
影响胃肠道的癌症非常普遍，其发病率仍在上升。其中，胃癌和胰腺癌的预后较差（5-20%的生存率），被定义为难治性癌症。这反映了对新型治疗靶点和个性化治疗的迫切需求。作为确定治疗靶点和测试治疗干预措施的前提，建立完善的、转化的和可靠的临床前研究模型是至关重要的。本文讨论了患者来源的类器官（PDO）和患者来源的异种移植物（PDX）在胃腺癌和胰腺导管腺癌（PDAC）中的发展、优势和局限性。第一代和第二代多细胞 PDO/PDX 模型被认为能够在临床前环境中真实地生成患者特异性模型，为这些难治性癌症开辟了新的治疗方向。令人兴奋的是，未来的机会，如 PDO 与免疫或基质细胞的共培养、类器官芯片模型和人源化 PDX，为一个全新的领域奠定了基础，提供了更接近人类的模型。这些工具可以用来理解癌症异质性，这对于为更具肿瘤特异性的治疗方法铺平道路是不可或缺的，从而为患者带来更好的生存机会。
