Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Department of Urology, Weill Cornell Medical College, New York, New York.
Curr Opin Urol. 2024 Jul 1;34(4):244-250. doi: 10.1097/MOU.0000000000001182. Epub 2024 Apr 16.
Bladder cancer (BC) is a highly heterogenous disease comprising tumours of various molecular subtypes and histologic variants. This heterogeneity represents a major challenge for the development of novel therapeutics. Preclinical models that closely mimic in vivo tumours and reflect their diverse biology are indispensable for the identification of therapies with specific activity in various BC subtypes. In this review, we summarize efforts and progress made in this context during the last 24 months.
In recent years, one main focus was laid on the development of patient-derived BC models. Patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) were demonstrated to widely recapitulate the molecular and histopathological characteristics, as well as the drug response profiles of the corresponding tumours of origin. These models, thus, represent promising tools for drug development and personalized medicine. Besides PDXs, syngenic in vivo models are of growing importance. Since these models are generated using immunocompetent hosts, they can, amongst others, be used to develop novel immunotherapeutics and to evaluate the impact of the immune system on drug response and resistance.
In the past two years, various in vivo and in vitro models closely recapitulating the biology and heterogeneity of human bladder tumours were developed.
膀胱癌(BC)是一种高度异质性疾病,包括各种分子亚型和组织学变异的肿瘤。这种异质性对新型治疗药物的开发构成了重大挑战。与体内肿瘤密切相似并反映其多种生物学特性的临床前模型对于鉴定对各种 BC 亚型具有特异性活性的治疗方法是必不可少的。在这篇综述中,我们总结了过去 24 个月中在这方面所做的努力和取得的进展。
近年来,人们主要关注开发患者来源的 BC 模型。已经证明患者来源的类器官(PDO)和患者来源的异种移植物(PDX)广泛重现了相应起源肿瘤的分子和组织病理学特征以及药物反应特征。因此,这些模型代表了药物开发和个性化医疗的有前途的工具。除了 PDX 之外,同种型体内模型的重要性也在不断增加。由于这些模型是使用免疫活性宿主生成的,因此它们可以用于开发新型免疫疗法,以及评估免疫系统对药物反应和耐药性的影响。
在过去的两年中,已经开发出了各种能够很好地重现人类膀胱癌生物学和异质性的体内和体外模型。