通过激酶活性分析和达布拉芬尼BRAF V600E向向来区分良性和恶性甲状腺瘤
Riet Hilhorst1, Adrienne van den Berg1, Piet Boender1
1PamGene International BV, 5211 HH 's-Hertogenbosch, The Netherlands.
Cancers
|September 28, 2023
概括
氨酸/氨酸激酶活性概况准确地区分良性与恶性甲状腺瘤. 这种方法还确定了用于区分BRAF V600E突变型乳头甲状腺癌的特定,有助于向治疗选择.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 差异化非骨髓性甲状腺癌 (NMTC) 的复发与酸运输损失和BRAF V600E突变有关.
- 针对BRAF V600E突变的向疗法在NMTC中显示出可变的疗效.
- 仅靠下一代测序 (NGS) 可能无法完全预测治疗反应.
研究的目的:
- 评估氨酸/氨酸激酶 (STK) 活性概况,以对良性和恶性甲状腺病变进行分类.
- 确定特定的RAF抑制剂 (达布拉费尼布,索拉费尼布,雷戈拉费尼布) 是否可以区分BRAF V600E突变型与非突变型甲状腺瘤.
- 探索STK分析作为一种改善针对性治疗选择的工具,用于治疗复发性甲状腺癌.
主要方法:
- 在21个良性和34个恶性冷甲状腺瘤样本上使用PamChip®微阵列分析了血清蛋白/氨酸激酶活性.
- 开发一种STK活动分类器来区分瘤类型.
- 使用dabrafenib,sorafenib和regorafenib对BRAF V600E突变型和非突变型乳头甲状腺癌 (PTC) 的活体激酶抑制试验.
主要成果:
- 该STK活动分类器在区分恶性 (26/34) 和良性 (16/21) 甲状腺瘤方面取得了76%的准确性.
- PKC (甲基) 和PKD1在良性和恶性瘤之间显示出差异性活性;瘤细胞新生病和格雷夫斯病影响了分类.
- 达布拉费尼布发现了6/92,使BRAF V600E突变细胞与非突变细胞PTC区分开来,这种效应在索拉费尼布或雷戈拉费尼布中没有观察到.
结论:
- STK活动概况有效地区分良性与恶性甲状腺瘤,并产生对差异活性激酶的假设.
- 这种方法为选择基于组织分析的新激酶抑制剂提供了一个模型.
- 基于组织的激酶分析可能会提高针对性治疗的疗效,以治疗复发的甲状腺癌和其他癌症.
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