线素激活通路激酶抑制剂-关联视网膜病变:在上游与下游抑制方面,特征有所不同吗?
Jasmine H Francis1,2, William Foulsham1,2, Julia Canestraro1
1Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ocular oncology and pathology
|February 20, 2024
概括
线原激活通路激酶 (MAPK) 抑制剂可以导致视网膜病变. 这项研究发现,抑制MEK或ERK等下游目标会导致比抑制上游FGFR信号更严重的视网膜液积累.
科学领域:
- 在瘤学瘤学.
- 眼科医生 眼科 眼科
- 药理学 药理学是指药理学的学科.
背景情况:
- 线素激活通路激酶 (MAPK) 途径是许多癌症的治疗点.
- MAPK 抑制剂可能会导致不良反应,包括视网膜病变.
- 不同的MAPK抑制剂针对该途径中的不同点,可能导致各种副作用.
研究的目的:
- 在接受MAPK抑制剂与可变途径抑制的患者中,比较血清性视网膜障碍的临床和形态特征.
- 根据特定的MAPK路径目标 (FGFR,MEK或ERK) 调查视网膜病变严重程度的差异.
主要方法:
- 从单一的三级瘤学转诊中心前性收集数据的回顾性观察性研究.
- 包括65名患有转移性癌症的患者 (128只眼睛),接受了FGFR,MEK或ERK抑制剂治疗,通过光学连贯断层扫描 (OCT) 确认了视网膜病变.
- 基线OCT与治疗出现的胆管/视网膜OCT异常进行了比较.
主要成果:
- 视网膜病变表现为双边的,涉及,可逆的下液焦点在所有药物类别.
- 视网膜病变是最不常见的,最不严重的,和最不具有症状的上游FGFR抑制剂.
- 视网膜病变是最常见的,最严重的 (更多的流体焦点,膨胀的配置),最具症状的下游MEK或ERK抑制剂.
结论:
- MAPK 途径抑制剂可以诱导根据向蛋白 (FGFR,MEK,ERK) 具有独特特征的下液焦点.
- 进一步抑制MAPK通路的下游结果是视网膜病变的发病率更高,严重程度更大,症状增加.
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