在错配修复缺陷型癌症中用小分子靶向沃纳综合征解旋酶
Targeting Werner Syndrome Helicase with Small Molecules in Mismatch Repair-Deficient Cancers.
作者信息
Kargbo Robert B
机构信息
Usona Institute, Fitchburg, Wisconsin 53711-5300, United States.
出版信息
ACS Med Chem Lett. 2025 May 16;16(6):945-947. doi: 10.1021/acsmedchemlett.5c00262. eCollection 2025 Jun 12.
Abstract
Recent efforts have identified WRN helicase as a critical dependency in mismatch repair-deficient (dMMR) cancers. Small molecules targeting WRN demonstrate selective activity in microsatellite instability-high (MSI-H) models. These compounds impair tumor growth and promote cancer cell death by disrupting genome maintenance pathways, highlighting a promising therapeutic strategy for genetically defined, treatment-resistant tumors.
摘要
最近的研究发现，WRN解旋酶是错配修复缺陷（dMMR）癌症中的关键依赖因素。靶向WRN的小分子在微卫星高度不稳定（MSI-H）模型中表现出选择性活性。这些化合物通过破坏基因组维持途径来损害肿瘤生长并促进癌细胞死亡，凸显了一种针对基因定义的难治性肿瘤的有前景的治疗策略。
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