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In vitro human cell line models to predict clinical response to anticancer drugs

机译:体外人类细胞系模型预测抗癌药物的临床反应

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In vitro human cell line models have been widely used for cancer pharmacogenomic studies to predict clinical response, to help generate pharmacogenomic hypothesis for further testing, and to help identify novel mechanisms associated with variation in drug response. Among cell line model systems, immortalized cell lines such as Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) have been used most often to test the effect of germline genetic variation on drug efficacy and toxicity. Another model, especially in cancer research, uses cancer cell lines such as the NCI-60 panel. These models have been used mainly to determine the effect of somatic alterations on response to anticancer therapy. Even though these cell line model systems are very useful for initial screening, results from integrated analyses of multiple omics data and drug response phenotypes using cell line model systems still need to be confirmed by functional validation and mechanistic studies, as well as validation studies using clinical samples. Future models might include the use of patient-specificinducible pluripotent stem cells and the incorporation of 3D culture which could further optimize in vitro cell line models to improve their predictive validity.
机译:体外人类细胞系模型已广泛用于癌症药物基因组学研究,以预测临床反应,帮助产生药物基因组学假说以进一步测试,并帮助鉴定与药物反应变化相关的新机制。在细胞系模型系统中,最常使用永生化细胞系,例如爱泼斯坦-巴尔病毒(EBV)转化的淋巴母细胞系(LCL),来测试种系遗传变异对药物功效和毒性的影响。另一种模型,尤其是在癌症研究中,使用了癌细胞系,例如NCI-60面板。这些模型主要用于确定体细胞变化对抗癌治疗反应的影响。尽管这些细胞系模型系统对于初始筛选非常有用,但仍需要通过功能验证和机理研究以及使用临床的验证研究来确认使用细胞系模型系统对多种组学数据和药物反应表型进行综合分析的结果样品。未来的模型可能包括使用患者特异性可诱导的多能干细胞,并纳入3D培养物,这可以进一步优化体外细胞系模型以提高其预测效度。

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