新的小分子SERCA抑制剂提高了伦瓦提尼布抗性乳头甲状腺癌的治疗效率
Jungmin Kim1, Hang-Seok Chang2, Hyeok Jun Yun2
1Department of Surgery, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
International journal of molecular sciences
|October 16, 2024
概括
研究人员确定了sarco/endoplasmic reticulum ATPase (SERCA) 抑制剂,以对抗耐药性乳头甲状腺癌. 这些化合物与伦瓦提尼布结合,在减少瘤生长和细胞活力方面表现有前途.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 乳头甲状腺癌 (PTC) 是可以治疗的,但耐药性会导致转移和死亡.
- 转移性/复发性PTC中药物耐药性的机制,特别是通过表观遗传重编程,尚不清楚.
- 耐火性PTC是一个重大的临床挑战,需要新的治疗策略.
研究的目的:
- 为了确定增强治疗疗效的小分子抑制剂,在伦瓦提尼布抗性PTC中.
- 为了研究/内质网膜 ATPase (SERCA) 作为一种潜在的治疗点在耐药PTC.
主要方法:
- 分析患者衍生lenvatinib耐药与敏感PTC细胞中的SERCA水平.
- 在子选中识别SERCA抑制剂.
- 使用异种移植模型和细胞活力测试,评估与伦瓦提尼布联合使用的已识别的抑制剂.
主要成果:
- 在抗伦瓦提尼布的PTC细胞中观察到SERCA水平升高.
- 确定了两种SERCA抑制剂 (异花和乙烯酸).
- 与伦瓦提尼布和SERCA抑制剂的联合治疗在耐药PTC模型中显著降低了瘤大小和细胞活力.
结论:
- 在PTC中,SERCA是克服伦瓦替尼抗性的潜在治疗标.
- 塞尔卡抑制剂显示出作为一种新型组合治疗耐火性,高度恶性PTC的前景.
- 这些发现支持开发新的策略来治疗耐药癌症.
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