Department of Chemistry, Chung Yuan Christian University, Chung-Li 32023, Taiwan.
Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan.
Int J Mol Sci. 2018 Dec 7;19(12):3929. doi: 10.3390/ijms19123929.
Animal models play important roles in investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic tools. Despite rapid progress in the understanding of disease mechanisms and technological advancement in drug discovery, negative trial outcomes are the most frequent incidences during a Phase III trial. Skin cancer is a potential life-threatening disease in humans and might be medically futile when tumors metastasize. This explains the low success rate of melanoma therapy amongst other malignancies. In the past decades, a number of skin cancer models in fish that showed a parallel development to the disease in humans have provided important insights into the fundamental biology of skin cancer and future treatment methods. With the diversity and breadth of advanced molecular genetic tools available in fish biology, fish skin cancer models will continue to be refined and expanded to keep pace with the rapid development of skin cancer research. This review begins with a brief introduction of molecular characteristics of skin cancers, followed by an overview of teleost models that have been used in the last decades in melanoma research. Next, we will detail the importance of the zebrafish () animal model and other emerging fish models including platyfish ( sp.), and medaka () in future cutaneous malignancy studies. The last part of this review provides the recent development and genome editing applications of skin cancer models in zebrafish and the progress in small molecule screening.
动物模型在研究癌症的病理生物学、确定相关途径以及开发新的治疗工具方面发挥着重要作用。尽管在疾病机制的理解和药物发现的技术进步方面取得了快速进展，但在 III 期试验中，负面试验结果是最常见的情况。皮肤癌是人类潜在的危及生命的疾病，当肿瘤转移时可能在医学上无法治疗。这解释了黑色素瘤治疗在其他恶性肿瘤中的低成功率。在过去的几十年中，许多在鱼类中表现出与人类疾病平行发展的皮肤癌模型为皮肤癌的基础生物学和未来的治疗方法提供了重要的见解。随着鱼类生物学中可用的先进分子遗传工具的多样性和广度，鱼类皮肤癌模型将不断得到完善和扩展，以跟上皮肤癌研究的快速发展。本综述首先简要介绍皮肤癌的分子特征，然后概述过去几十年中在黑色素瘤研究中使用的硬骨鱼类模型。接下来，我们将详细介绍斑马鱼（）动物模型和其他新兴鱼类模型（如平鳍美洲蟾鱼（）和青鳉（））在未来皮肤恶性肿瘤研究中的重要性。本综述的最后一部分提供了斑马鱼皮肤癌模型的最新发展和基因组编辑应用以及小分子筛选的进展。
