Patient-derived xenografts of non small cell lung cancer: resurgence of an old model for investigation of modern concepts of tailored therapy and cancer stem cells.

Patient-derived xenografts of non small cell lung cancer: resurgence of an old model for investigation of modern concepts of tailored therapy and cancer stem cells.
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非小细胞肺癌的患者衍生异种移植物:旧模型的复兴,用于研究定制治疗和癌症干细胞的现代概念。

DOI:
10.1155/2012/568567
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发表时间:
2012
影响因子:
--
通讯作者:
Roz L
Roz L
中科院分区:
其他
文献类型:
--
作者:
Moro M;Bertolini G;Tortoreto M;Pastorino U;Sozzi G;Roz L

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目前的化疗方案对大多数晚期实体肿瘤的治疗效果并不理想。因此,当务之急是设计新的治疗策略,优化患者选择,及早确定哪些人可以从现有的治疗中受益。小鼠模型是癌症新治疗策略临床前评估的最有价值的工具,其中,患者来源的异种移植模型(PDX)最近重新流行起来。这些通过将组织片段直接植入免疫功能低下的小鼠而获得的模型,在药物开发研究中具有巨大的潜力,因为它们在免疫组织化学标记和遗传变化方面都忠实地复制了患者的原始肿瘤,在对常见治疗方法的反应方面也保持了原始肿瘤的异质性,允许研究特定的细胞亚群,包括药物治疗后的变化。此外,PDX在小鼠体内仅在2-3代后就能完全替代小鼠基质,至少在数周内保持了人类微环境的某些方面,因此是研究肿瘤-微环境相互作用的一个有前途的模型。本文综述了我们目前对小鼠临床前肿瘤模型的认识,重点介绍了非小细胞肺癌患者来源的异种移植瘤及其与临床前和生物学研究的相关性。
Current chemotherapy regimens have unsatisfactory results in most advanced solid tumors. It is therefore imperative to devise novel therapeutic strategies and to optimize selection of patients, identifying early those who could benefit from available treatments. Mouse models are the most valuable tool for preclinical evaluation of novel therapeutic strategies in cancer and, among them, patient-derived xenografts models (PDX) have made a recent comeback in popularity. These models, obtained by direct implants of tissue fragments in immunocompromised mice, have great potential in drug development studies because they faithfully reproduce the patient's original tumor for both immunohistochemical markers and genetic alterations as well as in terms of response to common therapeutics They also maintain the original tumor heterogeneity, allowing studies of specific cellular subpopulations, including their modulation after drug treatment. Moreover PDXs maintain at least some aspects of the human microenvironment for weeks with the complete substitution with murine stroma occurring only after 2-3 passages in mouse and represent therefore a promising model for studies of tumor-microenvironment interaction. This review summarizes our present knowledge on mouse preclinical cancer models, with a particular attention on patient-derived xenografts of non small cell lung cancer and their relevance for preclinical and biological studies.
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