晚期尿路上皮癌中的 ATR 抑制。
ATR Inhibition in Advanced Urothelial Carcinoma.
机构信息
University of California at Davis School of Medicine, Department of Internal Medicine, Division of Hematology Oncology, Sacramento, California, United States of America.
University of California at Davis School of Medicine, Department of Biochemistry and Molecular Medicine, Sacramento, California, United States of America.
出版信息
Clin Genitourin Cancer. 2023 Apr;21(2):203-207. doi: 10.1016/j.clgc.2022.10.016. Epub 2022 Nov 4.
The ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase 1 (CHK1) pathway is intricately involved in protecting the integrity of the human genome by suppressing replication stress and repairing DNA damage. ATR is a promising therapeutic target in cancer cells because its inhibition could lead to an accumulation of damaged DNA preventing further replication and division. ATR inhibition is being studied in multiple types of cancer, including advanced urothelial carcinoma where there remains an unmet need for novel therapies to improve outcomes. Herein, we review preclinical and clinical data evaluating 4 ATR inhibitors as monotherapy or in combination with chemotherapy. The scope of this review is focused on contemporary studies evaluating the application of this novel therapy in advanced urothelial carcinoma.
ATR 激酶 1（CHK1）是共济失调毛细血管扩张症和 Rad3 相关（ATR）检查点激酶，它通过抑制复制应激和修复 DNA 损伤来保护人类基因组的完整性。ATR 是癌细胞中很有前途的治疗靶点，因为抑制 ATR 会导致损伤 DNA 的积累，从而阻止进一步的复制和分裂。目前正在多种类型的癌症中研究 ATR 抑制，包括高级尿路上皮癌，这种癌症仍然需要新型疗法来改善治疗效果。本文综述了评估 4 种 ATR 抑制剂作为单药或与化疗联合治疗的临床前和临床数据。本综述的范围集中在评估这种新型疗法在高级尿路上皮癌中的应用的当代研究。
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