Morsani College of Medicine, Department of Pathology and Cell Biology, Tampa, FL 33612, USA.
Morsani College of Medicine, Department of Pathology and Cell Biology, Tampa, FL 33612, USA; Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Cancer Lett. 2014 Mar 1;344(1):1-12. doi: 10.1016/j.canlet.2013.10.010. Epub 2013 Oct 22.
Over the last few decades, study of cancer in mouse models has gained popularity. Sophisticated genetic manipulation technologies and commercialization of these murine systems have made it possible to generate mice to study human disease. Given the large socio-economic burden of cancer, both on academic research and the health care industry, there is a need for in vivo animal cancer models that can provide a rationale that is translatable to the clinic. Such a bench-to-bedside transition will facilitate a long term robust strategy that is economically feasible and clinically effective to manage cancer. The major hurdles in considering mouse models as a translational platform are the lack of tumor heterogeneity and genetic diversity, which are a hallmark of human cancers. The present review, while critical of these pitfalls, discusses two newly emerging concepts of personalized mouse models called "Mouse Avatars" and Co-clinical Trials. Development of "Mouse Avatars" entails implantation of patient tumor samples in mice for subsequent use in drug efficacy studies. These avatars allow for each patient to have their own tumor growing in an in vivo system, thereby allowing the identification of a personalized therapeutic regimen, eliminating the cost and toxicity associated with non-targeted chemotherapeutic measures. In Co-clinical Trials, genetically engineered mouse models (GEMMs) are used to guide therapy in an ongoing human patient trial. Murine and patient trials are conducted concurrently, and information obtained from the murine system is applied towards future clinical management of the patient's tumor. The concurrent trials allow for a real-time integration of the murine and human tumor data. In combination with several molecular profiling techniques, the "Mouse Avatar" and Co-clinical Trial concepts have the potential to revolutionize the drug development and health care process. The present review outlines the current status, challenges and the future potential of these two new in vivo approaches in the field of personalized oncology.
在过去几十年中，使用小鼠模型研究癌症已经变得越来越流行。复杂的遗传操作技术和这些鼠类系统的商业化使得生成可用于研究人类疾病的小鼠成为可能。鉴于癌症对学术研究和医疗保健行业造成的巨大社会经济负担，需要有一种能够提供临床转化依据的体内动物癌症模型。这种从实验室到临床的转化将促进一种长期稳健的、经济可行且具有临床疗效的策略，以管理癌症。将小鼠模型作为转化平台存在的主要障碍是缺乏肿瘤异质性和遗传多样性，而这些正是人类癌症的标志。虽然本文对这些陷阱进行了批判性讨论，但仍介绍了两种新兴的个性化小鼠模型概念，即“小鼠替身”和临床合作试验。“小鼠替身”的开发涉及将患者的肿瘤样本植入小鼠体内，以便随后用于药物疗效研究。这些替身允许每个患者在体内系统中拥有自己的肿瘤，从而可以确定个性化的治疗方案，避免与非靶向化疗措施相关的成本和毒性。在临床合作试验中，使用基因工程小鼠模型（GEMMs）来指导正在进行的人类患者试验中的治疗。同时进行小鼠和患者试验，并将从小鼠系统中获得的信息应用于患者肿瘤的未来临床管理。同时进行的试验允许实时整合小鼠和人类肿瘤数据。结合几种分子分析技术，“小鼠替身”和临床合作试验的概念有可能彻底改变药物开发和医疗保健过程。本文概述了这两种新的体内方法在个性化肿瘤学领域的现状、挑战和未来潜力。
