Modeling Lung Cancer Evolution and Preclinical Response by Orthotopic Mouse Allografts
Modeling Lung Cancer Evolution and Preclinical Response by Orthotopic Mouse Allografts
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DOI：
10.1158/0008-5472.can-14-1606
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发表时间：
2014-11-01
期刊：
影响因子：
11.2
通讯作者：
Villanueva, Alberto
中科院分区：
文献类型：
--
作者：
Ambrogio, Chiara;Carmona, Francisco J.;Villanueva, Alberto
由于缺乏全面的体内纵向研究，癌症的演变过程仍然知之甚少。通过产生小鼠非小细胞肺癌(NSCLC)原代细胞系和配对的原代细胞系，我们提供了体内、依赖于时间的癌症恶化过程的详细描述。我们确定了转移扩散潜能的获得，共同驱动突变的选择，以及自然发生的肿瘤内异质性的出现，从而概括了人类癌症发展的随机性质。这种方法结合了基因工程癌症模型的健壮性和同种异体移植方法学的灵活性。我们已经将这一工具应用于治疗方法的临床前评估。该系统可用于改进非小细胞肺癌患者未来治疗方案的设计。(C)2014年AACR。
Cancer evolution is a process that is still poorly understood because of the lack of versatile in vivo longitudinal studies. By generating murine non-small cell lung cancer (NSCLC) orthoallobanks and paired primary cell lines, we provide a detailed description of an in vivo, time-dependent cancer malignization process. We identify the acquisition of metastatic dissemination potential, the selection of co-driver mutations, and the appearance of naturally occurring intratumor heterogeneity, thus recapitulating the stochastic nature of human cancer development. This approach combines the robustness of genetically engineered cancer models with the flexibility of allograft methodology. We have applied this tool for the preclinical evaluation of therapeutic approaches. This system can be implemented to improve the design of future treatments for patients with NSCLC. (C) 2014 AACR.