在软组织肉瘤中利用附带敏感性来演变对氨酸激酶抑制剂的耐药性
Mark L Elms1, Andrew D Jenks1, Avirup Chowdhury1
1Division of Cancer Biology, The Institute of Cancer Research, London, UK.
Communications biology
|August 9, 2025
概括
获得对多位氨酸激酶抑制剂 (mTKI) 的耐药性在软组织肉瘤 (STS) 中很常见. 这项研究揭示了对其他药物的附带敏感性,为STS患者的持久治疗反应提供了一个新的适应性治疗策略.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 癌症生物学 癌症生物学
背景情况:
- 广泛的多位氨酸激酶抑制剂 (mTKI) 已被批准用于软组织肉瘤 (STS) 治疗.
- 获得对mTKIs的耐药性是一个重大的临床挑战,限制了STS患者的持久治疗反应.
- 需要新的策略来克服mTKI耐药性并改善治疗结果.
研究的目的:
- 为了研究用mTKI治疗的STS细胞中的耐药性机制.
- 确定其他治疗策略,以克服获得的mTKI耐药性.
- 探索在STS中适应性治疗的附带敏感性的潜力.
主要方法:
- 在获得对临床相关的mTKI耐药性的STS细胞中评估交叉耐药性模式.
- 调查药物耐药性的获得过程中附带敏感性的发展.
- 评估利用附带敏感性与替代药物的有效性,特别是西特拉瓦提尼布和因菲格拉提尼布,用于适应性治疗.
主要成果:
- 对一种mTKI获得抗性的STS细胞对其它细胞呈现交叉抗性,并且连续治疗不会延迟抗性.
- 随着STS细胞对mTKIs获得耐药性,它们对替代药物产生附带敏感性.
- mTKI西特拉瓦替尼迅速诱导对FGFR抑制剂infigratinib的附带敏感性,这在适应性治疗方法中使用时有效抑制STS细胞生长.
结论:
- 抵押品敏感性是一个有前途的策略,可以克服STS中对mTKI的获得性阻力.
- 利用附带敏感性的自适应疗法可能提供一种新的方法,以在STS患者中实现持久的治疗反应.
- 对基于附带敏感性的适应性疗法进行进一步的临床探索对于mTKI耐药的STS来说是有必要的.
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