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Updated: Sep 17, 2025

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KEAP1/NRF2通路在非BRAF突变性甲状腺状细胞癌中的参与
Elin Schoultz1,2, Jakob Dahlberg1,3,4, Lisa M Nilsson1,3
1Sahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden.
The Journal of pathology
|July 2, 2025
概括
甲状腺状细胞癌 (SCC) 源于乳头甲状腺癌 (PTC),由KEAP1/NRF2路径突变驱动. 谷氨胺酶抑制剂对这种罕见的甲状腺腺癌 (ATC) 亚型的治疗有前途.
科学领域:
- 在瘤学瘤学.
- 分子病理学分子病理学
- 癌症遗传学 癌症遗传学
背景情况:
- 甲状腺状细胞癌 (SCC) 是一种罕见的亚塑性甲状腺癌 (ATC) 亚型,预后不佳,治疗选择有限.
- 它的起源和分子驱动因素不太清楚,一些证据表明它是从乳头甲状腺癌 (PTC) 进化而来的.
研究的目的:
- 提供甲状腺SCC从PTC衍生的直接证据.
- 为了阐明甲状腺SCC的分子病原性.
- 评估使用患者衍生异种移植 (PDX) 的甲状腺SCC向治疗方法.
主要方法:
- 对匹配的PTC和SCC瘤进行比较基因组分析.
- 免疫组织化学评估转差异化.
- 建立和描述甲状腺SCC PDX模型.
- 在体内使用PDX模型与向抑制剂的药物疗效研究.
主要成果:
- 通过KEAP1,STK11和RB1的突变支持PTC到SCC转基因差异化的直接证据.
- 成功建立了一个独特的甲状腺SCCPDX模型.
- 联合TRK/PI3K抑制 (卡博赞提尼布+GDC-0326) 和谷氨酸酶抑制 (CB-839) 显著降低了PDX瘤的生长.
- KEAP1/NRF2通路的异常激活被确定为甲状腺SCC的一个关键特征.
结论:
- 甲状腺SCC源于PTC,其特征是特定的突变和途径改变.
- 向疗法,特别是谷氨胺酶抑制,显示出治疗这种侵袭性甲状腺癌亚型的巨大潜力.
- KEAP1/NRF2通路是甲状腺SCC中的一个新的治疗点.
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