揭示内分泌治疗耐药HER2+/ER+乳腺癌的脆弱性
Shaymaa Bahnassy1, Hillary Stires2, Lu Jin1
1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC.
bioRxiv : the preprint server for biology
|September 4, 2023
概括
这项研究开发了内分泌治疗耐药HER2+/ER+乳腺癌的模型. 这些模型显示,向脂质代谢和铁亡,特别是GPX4,为这种具有挑战性的癌症亚型提供了潜在的治疗脆弱性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 人类表皮生长因子受体2 (HER2) 阳性乳腺癌 (BCa) 经常表现出对内分泌疗法 (ET) 的抗性.
- HER2阳性/雌激素受体阳性 (HER2+/ER+) BCa患者对ET的反应较低,这构成了临床挑战,特别是当ET作为单疗法使用时.
- 这项研究的目的是开发和描述ET-resistant (ETR) HER2+/ER+ BCa的实验室模型,以确定治疗脆弱性.
结论:
- 开发的BT474和MM361AI耐药模型代表了HER2+/ER+BCa的不同的表型.
- 改变的脂质代谢和铁灭重塑被确定为这一ETRBCa亚型的关键漏洞.
- 在两种ETR模型中,GPX4和HER2的联合抑制显著诱导了细胞死亡,这表明了潜在的治疗策略.
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