KRAS G12C inhibition and innate immune targeting.

KRAS G12C inhibition and innate immune targeting.
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KRAS G12C抑制与先天免疫靶向。

DOI:
10.1080/14728222.2021.1902991
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发表时间:
2021-03
影响因子:
5.8
通讯作者:
Barbie DA
Barbie DA
中科院分区:
医学2区
文献类型:
--
作者:
Tani T;Kitajima S;Conway EB;Knelson EH;Barbie DA

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KRAS突变通过改变细胞信号传导和肿瘤免疫微环境来驱动肿瘤发生。最近的研究表明,KRAS-G12 C共价抑制剂有望通过临床试验快速发展。这些药物与其他疗法(包括免疫检查点阻断(ICB))的测序和组合将受益于也解决免疫微环境的策略,以提高反应的持久性。本文综述了KRAS信号传导,并讨论了下游对细胞因子产生和肿瘤免疫微环境的影响。介绍了RAS靶向治疗,并对KRAS-G12 C及其免疫抑制肿瘤微环境的治疗靶向提供了展望。KRAS-G12 C共价抑制剂的可用性为靶向这种普遍存在的癌基因和设计更好的治疗组合以促进抗肿瘤免疫带来了希望。为了优先考虑临床试验的药物,需要对KRAS免疫抑制的机制有全面的了解。
KRAS mutations drive tumorigenesis by altering cell signaling and the tumor immune microenvironment. Recent studies have shown promise for KRAS-G12C covalent inhibitors, which are advancing rapidly through clinical trials. The sequencing and combination of these agents with other therapies including immune checkpoint blockade (ICB) will benefit from strategies that also address the immune microenvironment to improve durability of response. This paper reviews KRAS signaling and discusses downstream effects on cytokine production and the tumor immune microenvironment. RAS targeted therapy is introduced and perspectives on therapeutic targeting of KRAS-G12C and its immunosuppressive tumor microenvironment are offered. The availability of KRAS-G12C covalent inhibitors raises hopes for targeting this pervasive oncogene and designing better therapeutic combinations to promote anti-tumor immunity. A comprehensive mechanistic understanding of KRAS immunosuppression is required in order to prioritize agents for clinical trials.
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