通过将泛癌转录组学与药理反应相结合,对肝细胞母细胞瘤进行计算药物预测
Mario Failli1,2, Salih Demir3, Álvaro Del Río-Álvarez4
1Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy.
Hepatology (Baltimore, Md.)
|September 20, 2023
概括
新的计算方法确定了两个CDK9抑制剂,alvocidib和dinaciclib,作为侵袭性肝母细胞瘤 (HB) 儿科肝癌的有效治疗方法,为选择有限的患者提供了希望.
科学领域:
- 在瘤学瘤学.
- 计算生物学 计算生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 肝母细胞瘤 (HB) 是主要的儿科肝癌,罕见,但对于晚期的治疗选择有限.
- 目前的HB治疗可能会导致幸存者长期出现严重的副作用.
- 对于HB患者来说,急需新的和有效的治疗策略.
研究的目的:
- 使用计算方法识别用于肝细胞母细胞瘤 (HB) 的新药候选者.
- 评估预测药物在攻击性C2亚型HB的疗效.
- 通过实验模型验证计算预测.
主要方法:
- 利用了DrugSense计算平台,包括泛癌转录概况和药物反应数据.
- 评估了36种瘤类型和495种化合物的药物疗效.
- 使用患者衍生的异种移植模型 (体外和体内) 实验验证的顶级候选药物.
主要成果:
- 确定了两种循环素依赖性激酶9 (CDK9) 抑制剂的阿尔沃西迪布 (alvocidib) 和迪纳西基布 (dinaciclib),作为HB生长的强有力的抑制剂.
- 这些抑制剂对HB的攻击性C2分子亚型表现出特别高的疗效.
- 在HB患者中,高CDK9瘤表达与预后不佳显著相关.
结论:
- 使用泛癌数据进行计算性药物重新定位对于罕见的儿科癌症,如HB,是有效的.
- 这种方法可以指导临床医生为HB患者选择最佳治疗方法.
- 阿尔沃西迪布 (Alvocidib) 和迪纳西基布 (Dinaciclib) 显示出作为高风险HB的向治疗的前景.
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