为尤因肉瘤构建EWS-FLI1驱动的转基因小鼠模型面临的挑战。
Challenges in modeling EWS-FLI1-driven transgenic mouse model for Ewing sarcoma.
作者信息
Ramachandran Balaji, Rajkumar Thangarajan, Gopisetty Gopal
机构信息
Department of Molecular Oncology, Cancer Institute (W.I.A) No. 38, Sardar Patel Road, Adyar, Chennai 600036, India.
出版信息
Am J Transl Res. 2021 Nov 15;13(11):12181-12194. eCollection 2021.
Abstract
EWS-FLI1 is a master regulator of Ewing sarcoma (ES) oncogenesis. Although EWS-FLI1 represents a clear therapeutic target, targeted therapeutic inhibitors are lacking. Scientific literature has indicated accumulating information pertaining to EWS-FLI1 translocation, pathogenesis, function, oncogenic partnerships, and potential clinical relevance. However, attempts to develop EWS-FLI1-driven human-like ES mouse models or in systems ended up with limited success. Establishing such models as preclinical screening tools may accelerate the development of EWS-FLI1 targeted therapeutic inhibitors. This review summarizes the current scenario, which focuses on the limitations, challenges, and possible reasons for past failures in model development and also plausible alternatives.
摘要
EWS-FLI1是尤因肉瘤（ES）肿瘤发生的主要调节因子。尽管EWS-FLI1是一个明确的治疗靶点，但缺乏靶向治疗抑制剂。科学文献表明，有关EWS-FLI1易位、发病机制、功能、致癌伙伴关系及潜在临床相关性的信息不断积累。然而，尝试开发由EWS-FLI1驱动的类人ES小鼠模型或体外系统，最终取得的成功有限。建立此类模型作为临床前筛选工具可能会加速EWS-FLI1靶向治疗抑制剂的开发。本综述总结了当前的情况，重点关注模型开发中过去失败的局限性、挑战和可能原因，以及合理的替代方案。
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