Department of Urology, Kyoto University Graduate School of Medicine, 54 Kawaharacho Shogoin Sakyo-ku, Kyoto, 6068507, Japan.
Nat Rev Urol. 2017 May;14(5):267-283. doi: 10.1038/nrurol.2017.19. Epub 2017 Feb 21.
Lack of appropriate models that recapitulate the complexity and heterogeneity of urological tumours precludes most of the preclinical reagents that target urological tumours from receiving regulatory approval. Patient-derived xenograft (PDX) models are characterized by direct engraftment of patient-derived tumour fragments into immunocompromised mice. PDXs can maintain the original histology, as well as the molecular and genetic characteristics of the source tumour. Thus, PDX models have various advantages over conventional cell-line-derived xenograft (CDX) and other models, which has resulted in an increase in the use of urological tumour PDXs in the analysis of tumour biology and, importantly, for drug development and treatment decisions in personalized medicine. PDX models of urological malignancies have great potential to be used for both basic and clinical research, but limitations exist and need to be overcome. In particular, several agents targeting the immune system have shown promising results in kidney and bladder cancer; however, establishing PDX models in mice with an intact immune system so that an immune response against the tumour is triggered is important to investigate these new therapeutics. Moreover, international collaboration to share PDX models is essential for research concerning fatal urological tumours.
缺乏能够重现泌尿系统肿瘤复杂性和异质性的合适模型,使得大多数针对泌尿系统肿瘤的临床前试剂无法获得监管部门的批准。患者来源的异种移植(PDX)模型的特点是直接将患者来源的肿瘤组织片段植入免疫缺陷小鼠体内。PDX 可以保持来源肿瘤的原始组织学以及分子和遗传特征。因此,PDX 模型相对于传统的细胞系来源的异种移植(CDX)和其他模型具有多种优势,这导致在肿瘤生物学分析中越来越多地使用泌尿系统肿瘤 PDX,并且对于药物开发和个性化医学中的治疗决策也很重要。泌尿系统恶性肿瘤的 PDX 模型具有在基础和临床研究中广泛应用的巨大潜力,但存在局限性,需要克服。特别是,几种针对免疫系统的药物在肾癌和膀胱癌中显示出了很有前景的结果;然而,在免疫系统完整的小鼠中建立 PDX 模型,以触发针对肿瘤的免疫反应,对于研究这些新疗法非常重要。此外,国际合作分享 PDX 模型对于致命性泌尿系统肿瘤的研究至关重要。