在翻译研究中,激酶抑制剂的过度度阻碍了有效的药物重定向
Chuan Liu1, Scott M Leighow2, Kyle McIlroy2
1Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA; Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Cell reports. Medicine
|October 18, 2023
概括
通过测量有效的药物暴露,可以改善药物重新定位. 这一新指标预测了白血病和固体瘤中酶抑制剂的临床成功,减少了晚期试验失败.
科学领域:
- 药理学和药物发现
- 瘤学和癌症研究研究.
- 翻译医学是一种翻译医学.
背景情况:
- 药物重新定位旨在为现有药物找到新的用途,但在临床试验的后期阶段经常面临高失败率.
- 激酶抑制剂是药物的关键类别,许多药物被评估为在各种疾病中重新定位.
研究的目的:
- 通过测量有效的药物暴露来开发药物重新定位成功的预测指标.
- 为了减少对激酶抑制剂的药物重定向研究中的临床失败率.
主要方法:
- 数据挖掘被用来分析139个重新定位假设,用于11个已批准的激酶抑制剂.
- 开发了一种体外药理动力学试验,结合人体血清蛋白来测量有效的药物暴露.
- 这一指标的预测能力在多种激酶抑制剂和癌症类型 (白血病,NSCLC,GIST) 中得到了验证.
主要成果:
- 开发的有效药物暴露指标对白血病中五种激酶抑制剂的临床活性具有很高的预测性.
- 模型的性能在6种额外的激酶抑制剂中进一步得到验证,用于非小细胞肺癌 (NSCLC) 和胃肠道 stromal 瘤 (GIST).
- 与传统的重新定位努力相比,这种方法在预测临床疗效方面显著改善.
结论:
- 使用校正的体外试验法测量有效药物暴露是一种简单有效的策略,可以提高药物重新定位的成功率.
- 这种方法可以降低临床失败率,使药物再利用成为开发新癌症疗法的更可靠策略.
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