https://scholars.lib.ntu.edu.tw/handle/123456789/637482
標題: | An activity-based functional test for identifying homologous recombination deficiencies across cancer types in real time | 作者: | Lee, Chih-Ying WEN-FANG CHENG PO-HAN LIN YU-LI CHEN Huang, Shih-Han Lei, Kai-Hang Chang, Ko-Yu Ko, Min-Yu HUNG-YUAN CHI |
關鍵字: | BRCA; DNA repair activity; DNA repair deficiency; HRD; PARP inhibitor; breast cancer; colorectal cancer; functional test; ovarian cancer | 公開日期: | 21-十一月-2023 | 出版社: | Cell Press | 卷: | 4 | 期: | 11 | 起(迄)頁: | Article number 101247 | 來源出版物: | Cell reports. Medicine | 摘要: | Homologous recombination (HR)-mediated DNA repair is a prerequisite for maintaining genome stability. Cancer cells displaying HR deficiency (HRD) are selectively eliminated by poly(ADP-ribose) polymerase inhibitors (PARPis). To date, sequencing of HR-associated genes and analyzing genome instability have been used as clinical predictions for PARPi therapy. However, these genetic tests cannot reflect dynamic changes in the HR status. Here, we have developed a virus- and activity-based functional assay to quantify real-time HR activity directly. Instead of focusing on a few HR-associated genes, our functional assay detects endpoint HR activity and establishes an activity threshold for identifying HRD across cancer types, validated by PARPi sensitivity and BRCA status. Notably, this fluorescence-based assay can be applied to primary ovarian cancer cells from patients to reflect their level of HRD, which is associated with survival benefits. Thus, our work provides a functional test to predict the response of primary cancer cells to PARPis. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637482 | ISSN: | 26663791 | DOI: | 10.1016/j.xcrm.2023.101247 |
顯示於: | 生化科學研究所 |
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