Wang Katharina, Fischer Alessa, Maccio Umberto, Hantel Constanze, Beuschlein Felix, Grossman Ashley B, Pacak Karel, Nölting Svenja
Department of Internal Medicine IV, LMU University Hospital, LMU Munich, 80336 Munich, Germany.
Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), CH-8091 Zurich, Switzerland.
Best Pract Res Clin Endocrinol Metab. 2024 Dec;38(6):101913. doi: 10.1016/j.beem.2024.101913. Epub 2024 Jul 4.
While the establishment of human phaeochromocytoma and paraganglioma (PPGL) cell lines has proven to be particularly difficult over several decades of research, there are other reliable pre-clinical PPGL models currently available. This review provides a summary of these models, together with our recently established personalised drug screening platform using patient-derived PPGL primary cultures. Such currently available PPGL models include murine and rat PPGL cell lines, of which only one cell line (PC12) is publicly accessible through a cell repository, and PPGL animal models, of which the patient-derived xenograft models are promising but complex to establish. We have developed next-generation implementation of human PPGL primary cultures, enabling reliable and personalised drug screening and an individualised analysis of tumour drug responsivity based on the tumour's unique genetic, biochemical, immunohistochemical and clinical profile. Overall, reliable PPGL models, including patient-derived primary culture models, are essential to advance pre-clinical research in the field of PPGLs.
尽管几十年来的研究已证明建立人嗜铬细胞瘤和副神经节瘤(PPGL)细胞系特别困难,但目前有其他可靠的临床前PPGL模型。本综述总结了这些模型,以及我们最近建立的使用患者来源的PPGL原代培养物的个性化药物筛选平台。目前可用的此类PPGL模型包括小鼠和大鼠PPGL细胞系,其中只有一种细胞系(PC12)可通过细胞库公开获取,还有PPGL动物模型,其中患者来源的异种移植模型很有前景,但建立起来很复杂。我们已经开发了人PPGL原代培养物的下一代实施方案,能够进行可靠的个性化药物筛选,并基于肿瘤独特的基因、生化、免疫组化和临床特征对肿瘤药物反应性进行个体化分析。总体而言,可靠的PPGL模型,包括患者来源的原代培养模型,对于推进PPGL领域的临床前研究至关重要。