CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer
Abstract: Poly (ADP‐ribose) Polymerase inhibitors (PARPi) have demonstrated remarkable clinical efficacy in treating ovarian cancer (OV) with BRCA1/2 mutations. However, drug resistance inevitably limits their clinical applications and there is an urgent need for improved therapeutic strategies to enhance the clinical utility of PARPi, such as Olaparib. Here, compelling evidence indicates that sensitivity of PARPi is associated with cell cycle dysfunction. Through high‐throughput drug screening with a cell cycle kinase inhibitor library, XL413, a potent cell division cycle 7 (CDC7) inhibitor, is identified which can synergistically enhance the anti‐tumor efficacy of Olaparib. Mechanistically, the combined administration of XL413 and Olaparib demonstrates considerable DNA damage and DNA replication stress, leading to increased sensitivity to Olaparib. Additionally, a robust type‐I interferon response is triggered through the induction of the cGAS/STING signaling pathway. Using murine syngeneic tumor models, the combination treatment further demonstrates enhanced antitumor immunity, resulting in tumor regression. Collectively, this study presents an effective treatment strategy for patients with advanced OV by combining CDC7 inhibitors (CDC7i) and PARPi, offering a promising therapeutic approach for patients with limited response to PARPi.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer ; day:16 ; month:10 ; year:2024 ; extent:17
Advanced science ; (16.10.2024) (gesamt 17)
- Urheber
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Liu, Shini
Deng, Peng
Yu, Zhaoliang
Hong, Jing Han
Gao, Jiuping
Huang, Yulin
Xiao, Rong
Yin, Jiaxin
Zeng, Xian
Sun, Yichen
Wang, Peili
Geng, Ruizi
Chan, Jason Yongsheng
Guan, Peiyong
Yu, Qiang
Teh, Bin‐Tean
Jiang, Qingping
Xia, Xiaojun
Xiong, Ying
Chen, Jianfeng
Huo, Yongliang
Tan, Jing
- DOI
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10.1002/advs.202403782
- URN
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urn:nbn:de:101:1-2410161441175.873733315283
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:21 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Liu, Shini
- Deng, Peng
- Yu, Zhaoliang
- Hong, Jing Han
- Gao, Jiuping
- Huang, Yulin
- Xiao, Rong
- Yin, Jiaxin
- Zeng, Xian
- Sun, Yichen
- Wang, Peili
- Geng, Ruizi
- Chan, Jason Yongsheng
- Guan, Peiyong
- Yu, Qiang
- Teh, Bin‐Tean
- Jiang, Qingping
- Xia, Xiaojun
- Xiong, Ying
- Chen, Jianfeng
- Huo, Yongliang
- Tan, Jing
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