对上腺皮癌的药物基因组分析揭示了与米托坦敏感性和潜在治疗方法相关的遗传特征
Jie Zhang1, Luming Wu1, Tingwei Su1
1Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Frontiers in endocrinology
|May 23, 2024
概括
来自患者的上腺皮质癌细胞对米托坦的反应有所变化. 脂质代谢途径和特定的基因表达,如CYP27A1和ABCA1,可以预测治疗的成功,建议新的治疗途径.
科学领域:
- 内分泌学 在内分泌学.
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 皮上腺癌 (ACC) 是一种具有有限治疗选择的侵袭性内分泌癌症.
- 米托坦是高级ACC的标准疗法,但其有效性难以预测.
- 预测米托坦反应和确定替代疗法对于改善患者的治疗结果至关重要.
研究的目的:
- 在体外使用患者衍生ACC细胞 (PDC) 评估mitotane的疗效.
- 在ACC中识别与米托坦反应相关的分子生物标志物.
- 探索针对ACC的潜在新型治疗剂.
主要方法:
- 在实验室中对17个PDC进行了米托坦敏感性测试.
- 在8个PDC中对40种化合物进行了高通量选.
- 外基因和转录基因测序用于分析9个样本中的遗传特征.
主要成果:
- PDCs对米托坦具有可变的敏感性,响应者显示显著较低的IC50和AUC值.
- 基因组分析揭示了响应者的CTNNB1变化和非响应者的ZNRF3变化.
- 在响应者中,脂质代谢途径被上调,而CYP27A1和ABCA1的表达与米托敏感性相关. 迪苏尔菲拉姆,尼克洛萨米德和博尔特佐米布对PDCs显示出有效性.
结论:
- ACC PDCs对于药物反应测试,药物重新定位和指导个性化治疗非常有价值.
- 米托坦反应可能与脂质代谢依赖有关.
- 作为预测标记物和潜在治疗药物,CYP27A1,ABCA1,dissulfiram,niclosamide和 bortezomib需要进一步研究.
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