在乳腺癌中对抗雌激素治疗的治疗耐药性
Marie Will1,2, Jackson Liang3, Ciara Metcalfe4
1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature reviews. Cancer
|July 27, 2023
概括
雌激素受体-α (ER) 在乳腺癌中至关重要. 在抗雌激素治疗期间,ER基因 (ESR1) 发生突变,导致治疗耐药性,需要新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 雌激素受体-α (ER) 信号传递对乳腺发育和乳腺癌至关重要.
- ER对抗是一种成功的疗法,但面临阻力.
- 在治疗压力下乳腺癌的演变是一个重大的临床挑战.
研究的目的:
- 在抗雌激素治疗下阐明推动乳腺癌演变的分子机制.
- 了解转移性乳腺癌中ESR1突变的患病率和影响.
- 为治疗耐药ER+乳腺癌的新型治疗策略的开发提供信息.
主要方法:
- 在原发性与转移性乳腺癌样本中分析ESR1基因突变.
- 在抗雌激素抵抗的背景下,研究ER信号通路.
- 评估下一代ER抗剂的临床疗效.
主要成果:
- 导致雌激素独立ER活性的ESR1突变在初级瘤中罕见,但在抗雌激素治疗后转移性疾病中流行 (20-40%).
- 这些突变表明ER阳性乳腺癌在治疗压力下的"可变性".
- 开发和批准了针对ESR1突变的下一代ER抗剂,证明了其临床重要性.
结论:
- 阳性ER乳腺癌具有显著的进化性,特别是通过ESR1突变,导致治疗耐药性.
- 了解这些进化过程对于克服治疗失败至关重要.
- 针对ESR1突变的向疗法代表了管理先进ER+乳腺癌的新范式.
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