针对FGFR的治疗方法:临床活性,抵抗机制和新方向
Masuko Katoh1, Yohann Loriot2,3, Giovanni Brandi4,5
1M & M Precision Medicine, Tokyo, Japan.
纤维细胞生长因子受体 (FGFR) 抑制剂在癌症治疗中至关重要,但面临副作用和耐药性等挑战. 下一代FGFR抑制剂旨在提高疗效并降低毒性,以改善患者的治疗结果.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物开发 药物开发
背景情况:
- 纤维细胞生长因子 (FGF) 通过FGF受体 (FGFR1-4) 发出信号,对发育和稳态至关重要,但异常信号驱动瘤发生.
- 目前的FGFR抑制剂 (erdafitinib,futibatinib,infigratinib,pemigatinib) 已被批准用于治疗特定癌症,如泌尿腺癌和胆管癌.
- 临床益处受到高酸血症 (非目标FGFR1抑制) 和获得的抗性机制 (突变,绕道通路,TP53改变) 的限制.
研究的目的:
- 审查FGFR抑制剂在癌症治疗中的发展和当前临床应用.
- 讨论新出现的耐药性机制和现有疗法的局限性.
- 为优化FGFR抑制剂治疗提供未来研究方向的观点.
主要方法:
- 审查关于FGFR抑制剂,其临床试验和作用机制的现有文献.
- 已批准的FGFR抑制剂及其治疗用处的分析.
- 讨论新兴的下一代抑制剂和新的治疗策略.
主要成果:
- 几种FGFR抑制剂已经获得了针对特定癌症类型的监管批准.
- 过酸血症和耐药性突变是显著的临床挑战.
- 下一代抑制剂 (lirafugratinib,LOXO-435) 和基于抗体的疗法 (bemarituzumab) 显示出克服这些局限性的前景.
结论:
- FGFR 抑制剂在向癌症治疗方面取得了重大进展.
- 解决耐药性和非目标毒性对于提高治疗疗效至关重要.
- 未来的研究应该集中在新型抑制剂,组合疗法 (例如,与免疫检查点抑制剂) 和扩展的指示.
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