个性化医学在囊性疾病:在没有MAPK变化的患者中创新目标
Katherine E R Smith1, Aldo A Acosta-Medina1, Surendra Dasari2
1Department of Hematology, Mayo Clinic, Rochester, MN.
JCO precision oncology
|November 22, 2024
概括
囊性疾病可能有非MAPK通路变化. 用特定的激酶抑制剂向这些新型遗传变化显示出持续患者反应的希望,即使在晚期病例中也是如此.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 药理学 药理学是指药理学的学科.
背景情况:
- 囊性疾病,包括埃尔德海姆-切斯特病 (ECD),通常用BRAF和MEK抑制剂治疗.
- 然而,一些患者缺乏MAPK通路的改变,导致治疗无效.
研究的目的:
- 在患有囊性疾病的患者中调查新的非MAPK通路变化.
- 评估针对性非标签激酶抑制剂对这些特定遗传变化的疗效.
主要方法:
- 进行了基因组和in silico分析,以确定三名患者的新遗传变异.
- 非标签的激酶抑制剂是根据已识别的基因组变化合理选择和管理的.
主要成果:
- 患有ECD的患者1获得了针对CSF1R删除的pexidartinib的完整反应,但后来发展了耐药性和转化为囊细胞肉瘤.
- 患有桑托格兰瘤疾病的患者2获得了针对KIF5B-FGFR1融合的佩米加替尼的部分反应,维持了24个月.
- 患有ECD的患者3在30个月的时间内,通过针对MEF2C-FLT3融合的索拉芬尼,实现了持续的完全和部分反应.
结论:
- 在囊胞性疾病中的新型非MAPK通路改变可以通过特定的激酶抑制剂有效地向.
- 这些发现表明,利用可用的小分子向MAPK途径之外的致病变体,包括意义不明的变体,是一种可行的治疗策略.
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