Huiting L N, Laroche Fjf, Feng H
Departments of Pharmacology and Medicine, Cancer Research Center, Section of Hematology and Medical Oncology, Boston University School of Medicine, Boston, MA, USA.
Austin J Pharmacol Ther. 2015;3(2):1069. Epub 2015 May 4.
The ability of zebrafish to faithfully recapitulate a variety of human cancers provides a unique system for drug identification and validation. Zebrafish models of human cancer generated through methodologies such as transgenesis, gene inactivation, transplantation, and carcinogenic induction have proven similar to their human counterparts both molecularly and pathologically. Suppression of cancer-relevant phenotypes provides opportunities to both identify and evaluate efficacious compounds using embryonic and adult zebrafish. After relevant compounds are selected, preclinical evaluation in mammalian models can occur, delivering lead compounds to human trials swiftly and rapidly. The advantages of imaging, large progeny, and rapid development that the zebrafish provides make it an attractive model to promote novel cancer drug discovery and reduce the hurdles and cost of clinical trials. This review explores the current methodologies to model human cancers in zebrafish, and how these cancer models have aided in formation of novel therapeutic hypotheses.
斑马鱼忠实地重现多种人类癌症的能力为药物鉴定和验证提供了一个独特的系统。通过转基因、基因失活、移植和致癌诱导等方法生成的人类癌症斑马鱼模型在分子和病理上已被证明与人类对应模型相似。癌症相关表型的抑制为使用胚胎和成年斑马鱼鉴定和评估有效化合物提供了机会。在选择相关化合物后，可以在哺乳动物模型中进行临床前评估，迅速将先导化合物推进到人体试验。斑马鱼所具有的成像、大量后代和快速发育等优势使其成为促进新型癌症药物发现以及降低临床试验障碍和成本的有吸引力的模型。本综述探讨了目前在斑马鱼中模拟人类癌症的方法，以及这些癌症模型如何有助于形成新的治疗假说。
