Patient-Derived Xenografts as a Model System for Radiation Research.
Patient-Derived Xenografts as a Model System for Radiation Research.
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DOI：
10.1016/j.semradonc.2015.05.008
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发表时间：
2015-10
影响因子：
3.5
通讯作者：
Gillespie GY
中科院分区：
文献类型：
--
作者：
Willey CD;Gilbert AN;Anderson JC;Gillespie GY
癌症文献充满了有希望的临床前研究，证明了新疗法的令人印象深刻的疗效，但这些方法转化为临床成功的情况很少，这表明目前用于预测疗效的方法是次优的。这些研究的局限性最可能的原因是临床前模型和临床治疗癌症之间的脱节。具体而言，大多数临床前模型对人类疾病的代表性较差。在癌症文献中占主导地位的永生化癌细胞系在某种意义上可能是“纸老虎”，它们是经过几十年的培养选择出来的，由高度靶向的蛋白质人工驱动。因此，尽管在体外或作为异种移植物从培养物移植到实验动物中的人工肿瘤有效治疗这些细胞系，但所鉴定的疗法在临床环境中可能表现不佳。这种固有的局限性不仅适用于药物测试，也适用于放射治疗实验。事实上，传统的放射生物学方法依赖于单层培养系统，重点是集落形成和DNA损伤评估，这可能限制了临床转化。因此，人们对开发肿瘤外植体系统非常感兴趣，其中使用免疫受损小鼠将患者肿瘤直接移植到体内并仅在体内维持。这些所谓的患者衍生异种移植物（PDX）代表了一种强大的模型系统，作为药物测试的上级临床前方法，该系统已获得学术界和工业界的支持。同样，PDX模型有可能改善辐射研究。在这篇综述中，我们描述了PDX模型目前如何用于药物和辐射测试，以及它们如何被纳入转化研究计划。
The cancer literature is filled with promising preclinical studies demonstrating impressive efficacy for new therapeutics, yet translation of these approaches into clinical successes has been rare, indicating that current methods used to predict efficacy are sub-optimal. The most likely reason for the limitation of these studies is the disconnect between preclinical models and cancers treated in the clinic. Specifically, most preclinical models are poor representations of human disease. Immortalized cancer cell lines that dominate the cancer literature may be, in a sense, “paper tigers” that have been selected by decades of culture to be artificially driven by highly targetable proteins. Thus, although effective in treating these cell lines either in vitro or as artificial tumors transplanted from culture into experimental animals as xenografts, the identified therapies will likely underperform in a clinical setting. This inherent limitation not only applies to drug testing, but also to experiments with radiation therapy. Indeed, traditional radiobiology methods rely on monolayer culture systems, with emphasis on colony formation and DNA damage assessment that may have limited clinical translation. As such, there has been keen interest in developing tumor explant systems in which patient tumors are directly transplanted into, and solely maintained in vivo, using immunocompromised mice. These so-called Patient-Derived Xenografts (PDX) represent a robust model system that has been garnering support in academia and industry as a superior preclinical approach to drug testing. Likewise, PDX models have the potential to improve radiation research. In this review, we describe how PDX models are currently being used for both drug and radiation testing and how they can be incorporated into a translational research program.