在芯片上模拟肝细胞癌及其微环境
Orsola Mocellin1, Stéphane Treillard1, Abbie Robinson1
1MIMETAS BV, De Limes 7, NL-2342DH, Oegstgeest, The Netherlands.
Cell death discovery
|December 29, 2025
概括
先进的肝细胞癌 (HCC) 患者衍生芯片模型显示,标准疗法不会影响瘤细胞,这凸显了对新药发现方法的需求. 这些模型有效地评估了瘤微环境中的药物反应.
科学领域:
- 在瘤学瘤学.
- 生物技术是生物技术.
- 药物发现 药物发现 药物发现
背景情况:
- 肝细胞癌 (HCC) 是一种流行性肝癌,发病率越来越高,与晚期肝病有关.
- 瘤微环境,包括细胞层和血管系统,极大地影响HCC的进展和治疗反应.
- 开发先进的模型对于HCC的早期药物和目标发现至关重要.
研究的目的:
- 使用血管化肝细胞癌患者衍生芯片 (PDChip) 模型进行表型查.
- 在PDChip模型中评估28种治疗条件对初级HCC瘤和细胞系的疗效.
- 评估药物对瘤细胞活力,与瘤相关的血管系统和化学因子/细胞因子概况的影响.
主要方法:
- 使用了大约1200个HCC PDChip,来自8个初级HCC瘤和2个细胞系.
- 在 perfusion 流下培养了 PDChip,并将其暴露在各种处理条件下.
- 评估结果包括细胞活力,血管床组织,以及化学激素和细胞激素释放的变化.
主要成果:
- 标准治疗方法 (sorafenib,lenvatinib) 降低了活力,但在PDChip模型中没有影响HCC瘤细胞.
- 阿托瓦斯塔丁降低了PDChip活力,但没有改变血管床组织.
- 几种测试药物调节了基因激素和细胞激素的释放,对IL6水平有显著的影响.
结论:
- HCC PDChip模型为评估瘤及其微观环境中的药物反应提供了一个强大的平台.
- 这些模型对临床前研究有价值,有助于了解疾病和开发新型HCC治疗方法.
- 该研究强调了当前治疗方法的局限性以及新药候选药物在调节HCC微环境方面的潜力.
相关概念视频
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02:17The Tumor Microenvironment
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...