Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations.
Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations.
复制标题
DOI：
10.1155/2016/4521807
复制
发表时间：
2016
影响因子：
--
通讯作者：
Herwig MC
中科院分区：
文献类型：
--
作者：
Stei MM;Loeffler KU;Holz FG;Herwig MC
动物模型是研究癌症病理生物学、识别相关通路和开发新型治疗药物的有力工具。它们促进了许多肿瘤实体的快速科学进步。然而，建立一个强大的葡萄膜黑色素瘤动物模型的基本挑战仍然存在。迄今为止，没有动物模型提供特定的遗传属性以及葡萄膜黑色素瘤的组织学，免疫学和转移特征。眼内注射皮肤黑色素瘤细胞的同基因模型可能最适合研究免疫学/肿瘤生物学方面。然而，皮肤黑色素瘤和葡萄膜黑色素瘤之间在遗传和转移方面的差异仍然存在问题。人类异种移植模型被广泛用于评估新的治疗方法，但需要免疫抑制以允许肿瘤生长。新的方法旨在建立自发性葡萄膜黑色素瘤的转基因小鼠模型，最近提供了初步的有希望的结果。每个模型都提供了某些好处，并可能使它们适合回答相应的科学问题。然而，所有现有的模型也表现出相关的局限性，这可能导致延迟的研究进展。尽管原发性眼部肿瘤的治疗方案不断完善，但自20世纪70年代以来，患者的预后并未改善。基础研究需要进一步集中在一个有效的动物模型，模仿葡萄膜黑色素瘤的进展和转移的具体机制的完善。本文将总结和解释现有的葡萄膜黑色素瘤的动物模型，包括在该领域的最新进展。
Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects. However, differences between cutaneous and uveal melanoma regarding genetics and metastasis remain problematic. Human xenograft models are widely used for evaluating novel therapeutics but require immunosuppression to allow tumor growth. New approaches aim to establish transgenic mouse models of spontaneous uveal melanoma which recently provided preliminary promising results. Each model provides certain benefits and may render them suitable for answering a respective scientific question. However, all existing models also exhibit relevant limitations which may have led to delayed research progress. Despite refined therapeutic options for the primary ocular tumor, patients' prognosis has not improved since the 1970s. Basic research needs to further focus on a refinement of a potent animal model which mimics uveal melanoma specific mechanisms of progression and metastasis. This review will summarise and interpret existing animal models of uveal melanoma including recent advances in the field.