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在癌症患者中准ATR

Natalie Y L Ngoi^1,2,3, Patrick G Pilié⁴, Daniel J McGrail⁵

¹Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Nature reviews. Clinical oncology

|February 20, 2024

概括

药理上抑制着阿塔克西亚 (ataxia telangiectasia) 和Rad3相关蛋白 (ATR) 激酶是一种有前途的癌症治疗方法. 需要进一步的研究来优化ATR抑制剂以获得更广泛的患者益处.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症治疗方法癌症治疗方法

背景情况:

ATAXIA telangiectasia和Rad3相关蛋白 (ATR) 激酶在DNA损伤修复和复制应激反应中起着至关重要的作用.
药物抑制ATR是癌症治疗中的新兴策略,在合成致死性和克服治疗耐药性方面表现有前途.

研究的目的:

审查ATR调节的分子机制及其临床相关性.
讨论开发ATR抑制剂用于癌症治疗的挑战和机遇.
探索ATR抑制剂在增强抗瘤免疫力和组合疗法的潜力.

主要方法:

本综述综合了关于ATR激酶抑制剂的当前研究.
它分析了各种固体癌症类型正在进行的临床试验的数据.
该审查整合了ATR与DNA修复途径和免疫系统相互作用的发现.

主要成果:

多种新型ATR抑制剂正在临床试验中,一些正在进入III期.
ATR抑制显示出利用合成致死性和克服治疗耐药性的潜力.
ATR抑制剂可以增强抗瘤免疫力,这表明在免疫治疗中发挥作用.

结论:

优化治疗指数和开发合理组合是ATR抑制剂的关键挑战.
更深入地了解预测生物标志物和类内差异对于患者选择至关重要.
对ATR复杂相互作用的进一步研究是必要的,以最大限度地提高其在癌症患者的临床益处.

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