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Current State of Animal (Mouse) Modeling in Melanoma Research

机译:黑色素瘤研究中动物(小鼠)建模的当前状态

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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.
机译:尽管在理解人类癌症的生物学和药物开发方面的技术进步方面取得了长足的进步,但是对于大多数患有包括黑素瘤在内的晚期疾病的癌症患者而言,治疗失败仍然是不可避免的结果。尽管FDA批准的针对晚期黑色素瘤的BRAF靶向疗法有很大希望,但快速耐药性的发展限制了其成功。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之一。下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改变。随着成功疗法的发展强烈依赖于临床相关的临床前模型以及新发现,已经产生了更先进的黑色素瘤模型。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模型,例如患者来源的肿瘤异种移植物,可局部诱导的BRAF小鼠模型和基于RCAS / TVA的模型,以及它们的优点和局限性。尽管经常批评小鼠黑素瘤模型不能很好地预测实验药物是否可以有效治疗,但是开发新的和更相关的模型可以在不久的将来解决这个问题。

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