One mouse, one patient paradigm: New avatars of personalized cancer therapy.
One mouse, one patient paradigm: New avatars of personalized cancer therapy.
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DOI：
10.1016/j.canlet.2013.10.010
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发表时间：
2014-03-01
期刊：
影响因子：
9.7
通讯作者：
Dave, Vrushank
中科院分区：
文献类型：
--
作者：
Malaney, Prerna;Nicosia, Santo V.;Dave, Vrushank
关键词：
在过去的几十年里，在老鼠模型上进行癌症的研究越来越受欢迎。复杂的基因操作技术和这些小鼠系统的商业化使制造小鼠研究人类疾病成为可能。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，需要体内动物癌症模型，以提供可移植到临床的理论基础。这种从病床到床边的过渡将促进长期稳健的战略，这种战略在经济上可行，在临床上有效地管理癌症。考虑将小鼠模型作为翻译平台的主要障碍是缺乏肿瘤异质性和遗传多样性，这是人类癌症的标志。目前的综述，虽然批评这些陷阱，讨论了两个新出现的概念的个性化小鼠模型称为“小鼠化身”和联合临床试验。开发“小鼠化身”需要将患者肿瘤样本植入小鼠体内，以便随后用于药物疗效研究。这些化身允许每个患者在体内系统中生长自己的肿瘤，从而能够识别个性化的治疗方案，消除与非靶向化疗措施相关的成本和毒性。在联合临床试验中，基因工程小鼠模型(GEMM)被用于指导正在进行的人类患者试验的治疗。小鼠和患者的试验是同时进行的，从小鼠系统获得的信息被应用于未来对患者肿瘤的临床治疗。同时进行的试验允许实时整合小鼠和人类的肿瘤数据。结合几种分子图谱技术，“小鼠阿凡达”和联合临床试验概念有可能彻底改变药物开发和医疗保健过程。本综述概述了这两种体内新方法在个性化肿瘤学领域的现状、挑战和未来潜力。
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.
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影响因子：
64.8
作者：
Chen, Zhao;Cheng, Katherine;Walton, Zandra;Wang, Yuchuan;Ebi, Hiromichi;Shimamura, Takeshi;Liu, Yan;Tupper, Tanya;Ouyang, Jing;Li, Jie;Gao, Peng;Woo, Michele S.;Xu, Chunxiao;Yanagita, Masahiko;Altabef, Abigail;Wang, Shumei;Lee, Charles;Nakada, Yuji;Pena, Christopher G.;Sun, Yanping;Franchetti, Yoko;Yao, Catherine;Saur, Amy;Cameron, Michael D.;Nishino, Mizuki;Hayes, D. Neil;Wilkerson, Matthew D.;Roberts, Patrick J.;Lee, Carrie B.;Bardeesy, Nabeel;Butaney, Mohit;Chirieac, Lucian R.;Costa, Daniel B.;Jackman, David;Sharpless, Norman E.;Castrillon, Diego H.;Demetri, George D.;Jaenne, Pasi A.;Pandolfi, Pier Paolo;Cantley, Lewis C.;Kung, Andrew L.;Engelman, Jeffrey A.;Wong, Kwok-Kin
通讯作者：
Wong, Kwok-Kin
影响因子：
45.3
作者：
Chakravarti, A;Zhai, G;Loeffler, JS
通讯作者：
Loeffler, JS
影响因子：
8.8
作者：
Garrido-Laguna, I.;Tan, A. C.;Hidalgo, M.
通讯作者：
Hidalgo, M.
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
11.2
作者：
Daniel VC;Marchionni L;Hierman JS;Rhodes JT;Devereux WL;Rudin CM;Yung R;Parmigiani G;Dorsch M;Peacock CD;Watkins DN
通讯作者：
Watkins DN