在3D生物打印瘤模型中评估一种新型泛RAS抑制剂
Daniela D De Nobrega1, Logan C Eiler1, Parmanand Ahirwar1
1CerFlux, Birmingham, AL 35203, USA.
Cancers
|September 27, 2025
概括
ADT-007,一种新的泛RAS抑制剂,在3D生物打印的ex vivo切片组织模型中显示出对KRAS突变结直肠癌 (CRC) 的强大和选择性疗效. 这种有针对性的方法为RAS驱动的癌症提供了有前途的治疗潜力.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 生物技术是生物技术.
背景情况:
- 结肠直肠癌 (CRC) 是一个主要的全球健康问题,在约40%的病例中存在KRAS突变.
- 目前的KRAS抑制剂由于抗性机制和特定的突变要求而面临局限性.
- 泛RAS抑制剂,如ADT-007,通过向多个RAS异型来呈现更广泛的治疗策略.
研究的目的:
- 为了评估泛RAS抑制剂ADT-007.7的疗效和选择性.
- 评估ADT-007在3D生物打印的ex vivo切片组织 (BEST) 模型中的活性,这些模型来自KRAS突变和野生型 (WT) CRC细胞系.
- 将ADT-007与现有治疗剂进行比较.
主要方法:
- 从CRC细胞系中利用3D生物打印的活体切片组织 (BEST) 模型.
- 通过使用高含量成像和基于ATP的发光测定来评估ADT-007的功效和选择性.
- 通过Annexin V/propidium iodide染色和流动细胞计量量化的亡诱导.
主要成果:
- 在KRAS突变BEST模型中,ADT-007表现出高强度和选择性,在纳米分子度下降了30%以上的瘤负担.
- 该药物在WT RAS BEST模型中表现出优越的选择性,细胞毒性最小.
- 附件V染色证实了KRAS突变细胞的选择性亡诱导.
结论:
- ADT-007的选择性疗效支持进一步调查RAS驱动癌症的泛RAS抑制剂.
- 3D BEST模型是临床前药物反应评估的宝贵工具.
- 使用患者衍生的BEST模型进行临床验证是需要确认ADT-007的治疗潜力.
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