PARP1
乳腺癌
癌症
PARP抑制剂
癌症研究
医学
帕博西利布
肿瘤科
聚ADP核糖聚合酶
内科学
生物
转移性乳腺癌
遗传学
聚合酶
基因
作者
Yu-zhou Huang,Ming‐Yi Sang,Pei-Wen Xi,Rener Xu,Mengyuan Cai,Z.J. Wang,Jianyi Zhao,Yi-Han Li,Ji‐Fu Wei,Qiang Ding
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2024-07-22
标识
DOI:10.1158/0008-5472.can-23-2738
摘要
Abstract Breast cancer is a global public health concern with high mortality rates, necessitating the development of innovative treatment strategies. PARP inhibitors have shown efficacy in certain patient populations, but their application is largely limited to cancers with homologous recombination deficiency. Here, we identified the suppression of FANCI as a therapeutic strategy to enhance the efficacy of PARP inhibitors in breast cancer. Elevated FANCI expression in breast cancer was associated with poor prognosis and increased cell proliferation and migration. FANCI interacted with PARP1, and suppressing FANCI limited the nuclear localization and functionality of PARP1. Importantly, FANCI inhibition sensitized breast cancer cells to the PARP inhibitor talazoparib in the absence of BRCA mutations. Additionally, the CDK4/6 inhibitor palbociclib enhanced the sensitivity of breast cancer cells to talazoparib through FANCI inhibition. These findings highlight the potential of targeting FANCI to enhance the efficacy of PARP inhibitors in treating breast cancer.
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