黑色素瘤动物(小鼠)模型研究现状

Cancer growth and metastasis Pub Date : 2015-10-06 eCollection Date: 2015-01-01 DOI:10.4137/CGM.S21214
Omer F Kuzu, Felix D Nguyen, Mohammad A Noory, Arati Sharma
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引用次数: 86

摘要

尽管在了解人类癌症的生物学和药物发现的技术进步方面取得了相当大的进展,但对于大多数晚期癌症患者,包括黑色素瘤,治疗失败仍然是不可避免的结果。尽管fda批准的braf靶向治疗晚期黑色素瘤显示出很大的希望,但快速耐药性的发展限制了成功。因此,与其他恶性肿瘤相比,黑色素瘤治疗的总体成功率仍然是最差的。新一代测序技术的进步可以更好地识别引发黑色素瘤发展的变异。由于成功疗法的开发在很大程度上依赖于临床相关的临床前模型,加上新的发现,更多的晚期黑色素瘤模型已经产生。在本文中,除了传统的黑色素瘤小鼠模型外,我们还将讨论最近的一些模型,如患者源性肿瘤异种移植、局部诱导BRAF小鼠模型和基于RCAS/ tva的模型,以及它们的优点和局限性。尽管黑色素瘤的小鼠模型经常被批评为不能很好地预测一种实验性药物是否能有效治疗,但在不久的将来,新的和更相关的模型的开发可以绕过这个问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Current State of Animal (Mouse) Modeling in Melanoma Research.

Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.

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