增长因子受体的可塑性推动了转移性乳腺癌的治疗持续性
Mitchell Ayers1,2, Marvis Monteiro1,2, Aneesha Kulkarni1,2
1Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
Cell death & disease
|April 4, 2025
概括
向纤维细胞生长因子受体 (FGFR) 使用佩米加替尼可能导致转移性乳腺癌 (MBC) 的最小残留疾病 (MRD). 将FGFR抑制与DNA甲基转移酶1 (DNMT1) 抑制相结合,可以克服这种抗性,改善结果.
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:
- 转移性乳腺癌 (MBC) 由于最小残留疾病 (MRD) 和复发而构成治疗挑战.
- 纤维细胞生长因子受体 (FGFR) 信号传递与MBC进展和治疗耐药性有关.
研究的目的:
- 研究FGFR抑制剂治疗的MBC中MRD和瘤复发的机制.
- 确定治疗策略,以克服治疗耐药性和改善MBC的结果.
主要方法:
- 使用了对FGFR抑制敏感的转移性乳腺癌的临床前模型.
- 在佩米加替尼治疗后评估受体表达 (PDGFR) 和细胞可塑性的变化.
- 研究了FGFR和DNA甲基转移酶1 (DNMT1) 抑制的有效性.
主要成果:
- 佩米加替尼的FGFR抑制导致肺病变的回归,但诱导了PDGFR上调的MRD.
- PDGFR信号传递有助于瘤在佩米加替尼治疗后复发.
- 联合抑制FGFR和DNMT1可以防止PDGFR诱导,增强瘤回归,并延长存活时间.
结论:
- 由PDGFR上调驱动的细胞可塑性在FGFR抑制后导致MBC复发.
- 联合FGFR和DNMT1抑制是克服MRD和提高MBC治疗疗效的有希望的策略.
- 向DNA甲基化可能会增强当前的MBC治疗方法.
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