在致癌,癌症治疗和抵抗机制中的RAS信号
Xiaojuan Yang1, Hong Wu2,3
1Liver Digital Transformation Research Laboratory, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China.
RAS突变在癌症中很常见,并且与糟糕的结果有关. 最近针对KRAS的疗法,如KRASG12C抑制剂,提供了新的希望,目前正在对其他RAS变体和抗药机制进行研究.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- RAS家族 (HRAS,NRAS,KRAS) 突变在大约19%的癌症中流行,与不良的临床预后相关.
- 从历史上看,由于其突变形式缺乏合适的结合点,KRAS被认为是无毒的.
- RAS信号通路在细胞信号传输中起着关键作用,在各种恶性瘤中经常受到失调.
研究的目的:
- 提供RAS信号通路及其在致癌过程中的参与的全面概述.
- 总结RAS突变在不同的人类癌症中的情况.
- 突出针对RAS突变的当前和新兴治疗策略,并解决抵抗机制.
主要方法:
- 文献综述和对RAS信号,突变和治疗方法现有研究的综合.
- 对有关RAS突变癌症的患病率和结果的临床数据的分析.
- 检查针对RAS向治疗的药物开发管道,包括KRASG12C和KRASG12D的抑制剂.
主要成果:
- 最近的进展导致了直接KRASG12C抑制剂 (例如,索托拉西布,阿达格拉西布) 的开发,这些抑制剂已被批准用于非小细胞肺癌 (NSCLC).
- 针对其他RAS突变的向疗法,如KRASG12D,正在开发中,特别是胰腺癌.
- 了解新的,获得的和适应性耐药性对于优化长期治疗疗效至关重要.
结论:
- 向RAS突变,曾经被认为是无法治疗的,现在是现实,已获得批准的疗法和有前途的候选药物.
- 对RAS信号传递,突变特征和抗性机制的持续研究对于推进癌症治疗至关重要.
- 新型治疗策略的开发具有显著的潜力,可以改善RAS突变癌症患者的治疗结果.
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