ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- The dual immune landscape of homologous recombination-deficient tumors: mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- RAD21 regulation of the enhancer-promoter chromatin loop of RAD51 promotes PARPi resistance in ovarian cancer.Journal of translational medicine · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Single-cell multiplex approaches deeply map ON-target CRISPR-genotoxicity and reveal its mitigation by palbociclib and long-term engraftment.Nature communications · 2026Article
- The cGAS-STING pathway in ovarian cancer: from genomic instability to immunotherapeutic vulnerability.Frontiers in immunology · 2026Review
- Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.Oncology research · 2026Review
- Priming with DNMT Inhibitors Potentiates PD-1 Immunotherapy by Triggering Viral Mimicry in Relapsed/Refractory NK/T-cell Lymphoma.Cancer discovery · 2025Article
- cGAS/STING signaling pathway in gynecological malignancies: From molecular mechanisms to therapeutic values.Frontiers in immunology · 2025Review
- CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
22 authors.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.