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在瘤克隆进化中利用时间附带敏感性
Boyang Zhao1, Joseph C Sedlak2, Raja Srinivas3
1Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|March 1, 2016
概括
癌症治疗可以利用瘤在药物耐药性进化过程中出现的脆弱性. 这项研究确定了对白血病新药的"时间附带敏感性",延长了小鼠的存活时间.
科学领域:
- 癌症学
- 癌症的演变
- 药理学
背景情况:
- 目前的癌症疗法通常用于治疗复发后的耐药性.
- 瘤克隆进化和相关的健康成本可能会产生可利用的漏洞.
- 这项研究引入了"时间附带敏感性"的概念.
研究的目的:
- 调查癌症药物耐药性的时间附带敏感性.
- 探索BCR-ABL1抑制剂耐药性的演变过程中产生的脆弱性.
- 确定针对动态瘤脆弱性的新疗法.
主要方法:
- 使用费城染色体阳性急性淋巴细胞白血病 (Ph ((+) ALL) 的小鼠模型.
- 使用药理查和药物耐药性选择方法.
- 综合基因型,表型,信号和结合测量与计算建模.
主要成果:
- 在耐药的Ph(+) ALL亚群中发现了对非经典BCR- ABL1药物的时间和持续的附带敏感性.
- 在接受治疗的小鼠中显著延长了整体生存期.
- 通过综合分析确定了敏感化机制.
结论:
- 时间附带敏感性代表了癌症发展中的有前途的治疗脆弱性.
- 专注于进化轨迹和药物药理特征可以揭示新的治疗策略.
- 这种方法有可能用于治疗血液恶性瘤的动态瘤脆弱性.
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