ArticleProceedings of the National Academy of Sciences of the United States of America2020
Rational combination therapy for hepatocellular carcinoma with PARP1 and DNA-PK inhibitors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 63 citations in OpenAlex.
- DNA-PKcs and PARP1 at the interface between DNA damage responses and cGAS-STING signaling: context-dependent roles and therapeutic implications.Cancer biology & therapy · 2026Review
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Computational and Experimental Verification of Cabozantinib Targeting DDX11 to Inhibit DNA Damage Repair in Liver Cancer.ACS omega · 2026Article
- Pan-cancer molecular signatures connecting aspartate transaminase to cancer prognosis, metabolic and immune signatures.Frontiers in oncology · 2026Article
- S100A9 promotes resistance to anti-PD-1 immunotherapy in hepatocellular carcinoma by degrading PARP1 and activating the STAT3/PD-L1 pathway.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- MK-8776 and Olaparib Combination Acts Synergistically in Hepatocellular Carcinoma Cells, Demonstrating Lack of Adverse Effects on Liver Tissues in Ovarian Cancer PDX Model.International journal of molecular sciences · 2025Article
- Article
- Downregulated TRAF3IP2-AS1 promotes hepatocellular carcinoma progression through the miR-374a-5p/SEL1L1/RPL6 axis to enhance DNA damage repair.American journal of translational research · 2025Article
- PARylation of HMGA1 desensitizes esophageal squamous cell carcinoma to olaparib.Clinical and translational medicine · 2024Article
- Disruption of RNA Splicing Increases Vulnerability of Cells to DNA-PK Inhibitors.International journal of molecular sciences · 2024Article
- Article
- KIN17 functions in DNA damage repair and chemosensitivity by modulating RAD51 in hepatocellular carcinoma.Human cell · 2024Article
- Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma.Molecular cancer therapeutics · 2024Article
- SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1-Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- Novel Techniques for Mapping DNA Damage and Repair in the Brain.International journal of molecular sciences · 2024Review
- DNA-PK participates in pre-rRNA biogenesis independent of DNA double-strand break repair.Nucleic acids research · 2024Article
- Acetylation-dependent regulation of core spliceosome modulates hepatocellular carcinoma cassette exons and sensitivity to PARP inhibitors.Nature communications · 2024Article
- NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.Cell genomics · 2024Article
- Rare-variant association study unveils the Achilles' heel for HCC.Cell genomics · 2024Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding differences in DNA double-strand break (DSB) repair between tumor and normal tissues would provide a rationale for developing DNA repair-targeted cancer therapy. Here, using knock-in mouse models for measuring the efficiency of two DSB repair pathways, homologous recombination (HR) and nonhomologous end-joining (NHEJ), we demonstrated that both pathways are up-regulated in hepatocellular carcinoma (HCC) compared with adjacent normal tissues due to altered expression of DNA repair factors, including PARP1 and DNA-PKcs. Surprisingly, inhibiting PARP1 with olaparib abrogated HR repair in HCC. Mechanistically, inhibiting PARP1 suppressed the clearance of nucleosomes at DNA damage sites by blocking the recruitment of ALC1 to DSB sites, thereby inhibiting RPA2 and RAD51 recruitment. Importantly, combining olaparib with NU7441, a DNA-PKcs inhibitor that blocks NHEJ in HCC, synergistically suppressed HCC growth in both mice and HCC patient-derived-xenograft models. Our results suggest the combined inhibition of both HR and NHEJ as a potential therapy for HCC.
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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.