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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Mini-Review Article

免疫疗法在转移性结直肠癌中的当前和不断发展的作用

卷 22, 期 8, 2022

发表于: 09 June, 2022

页: [617 - 628] 页: 12

弟呕挨: 10.2174/1568009622666220224110912

价格: $65

Open Access Journals Promotions 2
摘要

免疫疗法可以被认为是肿瘤学的一场治疗革命，对许多肿瘤类型有很大影响，例如黑色素瘤和非小细胞肺癌。然而，在转移性结直肠癌中，延长肿瘤控制和高反应率方面的益处仅限于具有高突变负荷的罕见肿瘤亚组——主要是具有微卫星不稳定性 (MSI) 或错配修复系统缺陷 (dMMR) 的肿瘤，或肿瘤微卫星稳定性和 POLE 或 POLD 的外切核酸酶结构域中的破坏性突变。 KEYNOTE-028 非对照 II 期试验表明，pembrolizumab 在治疗难治性 Lynch 相关肿瘤（包括结直肠癌）患者中具有令人印象深刻的抗肿瘤活性。 Nivolumab 联合或不联合 ipilimumab 证实了免疫检查点抑制剂对先前治疗的 dMMR / MSI 转移性结直肠癌患者的疗效。最近的 KEYNOTE-177 III 期试验表明，与使用或不使用生物制剂的一线化疗相比，pembrolizumab 显着降低了初治 dMMR / MSI 转移性结直肠癌患者的疾病进展或死亡的相对风险并提高了无进展生存期。不幸的是，目前免疫疗法的药理学策略对于大多数微卫星稳定转移性结直肠癌患者来说并不成功。在这篇综述中，我们批判性地评估了免疫检查点抑制剂在 dMMR/MSI 转移性结直肠癌中的适用性。我们还讨论了最近在微卫星稳定肿瘤中进行的免疫治疗组合的阴性试验以及在晚期结直肠癌领域正在进行的更成熟的免疫治疗研究。

关键词: 结直肠癌、免疫检查点抑制剂、免疫治疗、微卫星稳定性、微卫星不稳定性、单克隆抗体。

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