除了CDK4/6抑制剂之外,新兴的全身疗法选择用于激素受体阳性HER2-阴性晚期乳腺癌
Jun Ma1, Jack Junjie Chan1,2, Ching Han Toh1
1Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Singapore.
NPJ breast cancer
|September 8, 2023
概括
用循环素依赖性激酶4/6抑制剂 (CDK4/6i) 进行内分泌疗法 (ET) 是HR+,HER2-高级乳腺癌的标准. 本综述探讨了抗药性机制和克服它们的新治疗方法.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 内分泌疗法 (ET) 与循环素依赖性激酶4/6抑制剂 (CDK4/6i) 结合,是激素受体 (HR) 阳性,人体表皮生长因子受体 (HER2) 阴性先进乳腺癌的第一线标准.
- 获得对ET和CDK4/6i的耐药性是一个重大的临床挑战,需要制定有效的后进展治疗策略.
研究的目的:
- 审查在晚期乳腺癌中对ET和CDK4/6i产生抗性的机制.
- 总结最近的临床试验发现,针对针对抗性途径的新型治疗策略.
- 讨论瘤异质性和适应性抵抗在精准医学中的影响.
主要方法:
- 对临床前研究和临床试验的文献综述,研究对ET和CDK4/6i的抵抗机制.
- 对评估小分子抑制剂,抗体-药物合物和免疫治疗后进展的试验数据的分析.
- 综合关于信号通路,细胞循环调节和细胞死亡机制的信息.
主要成果:
- 抵抗机制涉及细胞循环介质的改变和替代信号通路的激活 (例如PI3K/AKT/mTOR,MAPK).
- 临床试验探讨了向雌激素/雌激素受体,FGFR,HER2和同源重组修复的临床试验.
- 新型药物显示出不同的临床益处,由于瘤异质性和毒性等因素,一些策略未能转化为显著的改善.
结论:
- 了解耐药机制对于开发有效的后进展疗法至关重要.
- 以个体瘤生物学为指导的精准医学方法对于克服治疗耐药性至关重要.
- 需要进一步的研究来开发具有改善治疗指数的新疗法,以对抗晚期乳腺癌的适应性耐药性.
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