Models for non-small cell lung carcinoma - part 2

NCI-H3122于1981年从治疗前的52岁男性中源于肺的原发性支气管血管癌。该细胞系患者将EML4-ALK融合蛋白（邻旋翼淋巴瘤激酶基因融合的ECHINODERM MICROTUBULE相关蛋白质4），并最近在〜7％的日本NSCLC（非小细胞肺癌）患者中鉴定了〜4.5所有NSCLC病例的百分比。ALK基因是赋予其致癌能力的目标靶标。由于NCI-H3122含有EML4-ALK并且对单剂ALK抑制剂具有高敏感性，因此其存活率通过更碱价的途径介导。²作为临床模yaboapp体育官网型，该细胞系适用于筛选不依赖于EGFR的新型烷基抑制剂，或者在NSCLC中涉及的其他途径。该模型已被开发为一个皮下来的(SC) implant; however, Covance has also implanted this line intracranially to mimic the clinical setting where advanced NSCLC metastasizes to the brain. Subcutaneous tumor growth is reliable with minimal animal-to-animal variability. The tumor volume doubling time in the SC setting is ~7 days and mice typically reach an evaluation size of ~750mm³大约25天。具有NCI-H3122的初始数据植入甲术术语是令人鼓舞的，在试验研究中，我们看到100％的率和肿瘤体积倍增时间，基于体积评估，〜7天，这与SC增长率一致（见图1和2）。与许多颅内模型一样，使用发病率（体重减轻和整体临床观察）来定义整体存活率。对于这种细胞系，死亡的中位数是〜35天（见图2,3和4）。

NCI-H1703

NCI-H1703 was derived from a stage 1 lung squamous cell carcinoma of a 54-year-old Caucasian male smoker. This cell line is of interest to the research community based on the high levels of platelet-derived growth factor receptor α (PDGFRα) amplification. NCI-H1703 is one of very few NSCLC models that have this expression profile and are sensitive to sunitinib体外。临床上，表达PDGFRα的肺癌患者与更积极的肿瘤生物学和更差的预后有关。³因此，该模型适用于评估新的血管生成靶标，例如VEGF以及独立于细胞表面增殖途径的新型PDGFRα靶标。该模型最常用于皮下（SC）植入后，然而，Covance也用荧光素酶转染了这条线以允许生物发光成像在直接植入肺部后监测疾病进展。肿瘤生长在SC或原位缺点（OT）肺部植入物。在两个植入物位点，动物对动物变异性最小，肿瘤体积倍增每6天（SC）和11天（OT）。虽然每个植入部位的肿瘤生长率不同，但小鼠通常达到评价尺寸（〜750mm³or 1.0E+09 p/s) in approximately 30 days post implant (See Figures 5 [SC], 6, 7, and 8 [OT]).

PC-9.

PC-9.was isolated from a male lung adenocarcinoma patient in 1989. PC-9 has been reported to be very sensitive to gefitinib and other EGFR tyrosine kinase inhibitors. However, it has been shown that prolonged exposure of PC-9 cells to EGFR inhibitors can result in acquisition of the T790M mutation and a resistant cell line. This model would be valuable when evaluating next generation EGFR inhibitors or possibly in the creation of a resistant version to evaluate alternative treatment approaches. Covance has developed PC-9 as a subcutaneous model that demonstrates reliable growth with minimal animal-to-animal variability. The tumor volume doubling time is ~7 days and the tumors typically reach evaluation size (~750mm³)在大约28days post implant (See Figures 9).

¹美国解除癌症研究。2016年AACR癌症进展报告。2016年临床癌症Res;22（补充1）：S1-S137。

²EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Jussi P. Koivunen, Craig Mermel, Kreshnik Zejnullahu, Carly Murphy, Eugene Lifshits,6 Alison J. Holmes, Hwan Geun Choi, Jhingook Kim, Derek Chiang, Roman Thomas, Jinseon Lee,9,10 William G. Richards, David J. Sugarbaker, Christopher Ducko, Neal Lindeman, J. Paul Marcoux, Jeffrey A. Engelman, Nathanael S. Gray, Charles Lee, Matthew Meyerson, and Pasi A. Jänne. Clin Cancer Res. 2008 Jul 1; 14(13): 4275–4283.

³基质血小板衍生的生长因子受体α（PDGFRα）提供肺癌异种移植物中肿瘤细胞PDGFRα表达的治疗靶标。David E. Gerber，Puja Gupta，Michael T. Dellinger，Jason E. Toombs，Michael Peyton，Inga Duignan，Jennifer Malaby，Timothy Bailey，Colleen Burns，Rolf A. Brekken和Nick Loizos分子癌症治疗方法10.1158 / 1535-7163.mct-12-0431 2012年11月发布。

⁴生成肺癌细胞系含EGFR / Cas9介导的Genome编辑Mi-Young Park，Min Hee Jung，Eun Young Eo，Seokjoong Kim，Sang Hoon Lee，Yeon Joo Lee，Jong Sun Park，Young Jae Cho，金航涌，Cheol Hyeon Kim，Ho Il Yoon，Jae Ho Lee，Choon-Taek Lee。oncotarget。2017年;8：36331-36338。https://doi.org/10.18632/oncotarget.16752。

^{注意：研究是根据AAALAC认可的设施中适用的动物福利法规进行的}

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