靶向癌症治疗中的 DNA 修复酶聚合酶θ。

Targeting the DNA Repair Enzyme Polymerase θ in Cancer Therapy.

机构信息

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria; Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.

出版信息

Trends Cancer. 2021 Feb;7(2):98-111. doi: 10.1016/j.trecan.2020.09.007. Epub 2020 Oct 24.

DOI:10.1016/j.trecan.2020.09.007

PMID:33109489

Abstract

Targeted cancer therapies represent a milestone towards personalized treatment as they function via inhibition of cancer-specific alterations. Polymerase θ (POLQ), an error-prone translesion polymerase, also involved in DNA double-strand break (DSB) repair, is often upregulated in cancer. POLQ is synthetic lethal with various DNA repair genes, including known cancer drivers such as BRCA1/2, making it essential in homologous recombination-deficient cancers. Thus, POLQ represents a promising target in cancer therapy and efforts for the development of POLQ inhibitors are actively underway with first clinical trials due to start in 2021. This review summarizes the journey of POLQ from a backup DNA repair enzyme to a promising therapeutic target for cancer treatment.

摘要

靶向癌症疗法代表了个性化治疗的一个里程碑，因为它们通过抑制癌症特异性改变起作用。聚合酶θ（POLQ）是一种易错的跨损伤聚合酶，也参与 DNA 双链断裂（DSB）修复，在癌症中经常上调。POLQ 与各种 DNA 修复基因（包括已知的癌症驱动基因，如 BRCA1/2）具有合成致死性，使其在同源重组缺陷型癌症中至关重要。因此，POLQ 是癌症治疗中一个很有前途的靶点，目前正在积极开发 POLQ 抑制剂，预计将于 2021 年开始首次临床试验。本综述总结了 POLQ 从备用 DNA 修复酶到癌症治疗有前途的治疗靶点的历程。