Duan Jie, Wang Yuan
Department of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and National Collaborative Innovation Center, Chengdu, 610041, China.
Cell Regen. 2023 Mar 1;12(1):4. doi: 10.1186/s13619-022-00150-7.
Nervous system cancers are the 10th leading cause of death worldwide, many of which are difficult to diagnose and exhibit varying degrees of treatment resistance. The limitations of existing cancer models, such as patient-derived xenograft (PDX) models and genetically engineered mouse (GEM) models, call for the development of novel preclinical cancer models to more faithfully mimic the patient's cancer and offer additional insights. Recent advances in human stem cell biology, organoid, and genome-editing techniques allow us to model nervous system tumors in three types of next-generation tumor models: cell-of-origin models, tumor organoids, and 3D multicellular coculture models. In this review, we introduced and compared different human stem cell/organoid-derived models, and comprehensively summarized and discussed the recently developed models for various primary tumors in the central and peripheral nervous systems, including glioblastoma (GBM), H3K27M-mutant Diffuse Midline Glioma (DMG) and H3G34R-mutant High-grade Glioma (HGG), Low-grade Glioma (LGG), Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2), Medulloblastoma (MB), Atypical Teratoid/rhabdoid Tumor (AT/RT), and meningioma. We further compared these models with PDX and GEM models, and discussed the opportunities and challenges of precision nervous cancer modeling with human stem cells and organoids.
神经系统癌症是全球第十大致死原因,其中许多难以诊断且表现出不同程度的治疗抗性。现有癌症模型,如患者来源的异种移植(PDX)模型和基因工程小鼠(GEM)模型存在局限性,这就需要开发新型临床前癌症模型,以更忠实地模拟患者的癌症并提供更多见解。人类干细胞生物学、类器官和基因组编辑技术的最新进展使我们能够在三种下一代肿瘤模型中模拟神经系统肿瘤:起源细胞模型、肿瘤类器官和三维多细胞共培养模型。在这篇综述中,我们介绍并比较了不同的人类干细胞/类器官衍生模型,并全面总结和讨论了最近针对中枢和外周神经系统中各种原发性肿瘤开发的模型,包括胶质母细胞瘤(GBM)、H3K27M突变型弥漫性中线胶质瘤(DMG)和H3G34R突变型高级别胶质瘤(HGG)、低级别胶质瘤(LGG)、1型神经纤维瘤病(NF1)、2型神经纤维瘤病(NF2)、髓母细胞瘤(MB)、非典型畸胎样/横纹肌样肿瘤(AT/RT)和脑膜瘤。我们进一步将这些模型与PDX和GEM模型进行了比较,并讨论了利用人类干细胞和类器官进行精准神经癌症建模的机遇与挑战。