缺陷不匹配修复/微卫星不稳定的结直肠癌:治疗进展和问题
Baptiste Cervantes1, Thierry André2,3, Romain Cohen2,4
1Department of Medical Oncology, Saint-Antoine Hospital, Sorbonne University, Paris, France AP-HP.
Therapeutic advances in medical oncology
|January 11, 2024
概括
微卫星不稳定性 (MSI) 测试对于结直肠癌 (CRC) 患者至关重要. 虽然抗PD1治疗是转移性CRC的标准,但研究正在探索组合和新辅助策略,以获得更好的结果.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 遗传学 是一个遗传学.
背景情况:
- 微卫星不稳定 (MSI) 现型,与DNA不匹配修复缺陷 (dMMR) 相关,影响5%的转移性结直肠癌 (mCRCs).
- 建议对所有结直肠癌 (CRC) 进行常规MSI/dMMR测试,不论其阶段如何.
- 免疫组织化学和聚合酶链反应是确定MSI/dMMR状态的可靠方法.
研究的目的:
- 审查MSI/dMMR mCRC中免疫检查点抑制剂 (ICI) 的当前情况.
- 讨论正在进行的组合疗法和新辅助/辅助ICI策略的研究.
- 突出抗药性挑战和预测生物标志物的需要.
主要方法:
- 对III期试验的审查,包括KEYNOTE 177.
- 对切除结肠癌中新辅助剂和辅助剂ICI使用数据的分析.
- 讨论早期进展的诊断考虑.
主要成果:
- 自2020年以来,布罗利祖马布 (抗PD1) 是MSI/dMMR mCRC的标准第一线治疗方法.
- 30-50%的MSI/dMMR mCRC患者经历了尽管使用抗PD1治疗,但进展.
- 新辅助性ICI显示出有希望的病理完整反应率,这表明"观察和等待"的可能性.
结论:
- 需要进一步的研究来验证MSI/dMMR mCRC中的组合疗法和双ICI策略.
- 目前缺乏针对抗PD1耐药性的预测生物标志物.
- 新辅助性ICI在早期疾病中提供了新的治疗范式的潜力.
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