ArticleEMBO molecular medicine2023
Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- PARP1 as a novel therapeutic and diagnostic tool in autoimmune rheumatic diseases: a systematic literature review.Rheumatology international · 2026Pooled it
- 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
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Recent advances of dual PROTACs for potential therapeutic applications.Molecular diversity · 2026Review
- PARP inhibitor YCH1899 activates type I interferon signaling and synergizes with STING agonists in BRCA-proficient tumors.Molecular biomedicine · 2026Article
- XYL-1 and Olaparib Synergistically Inhibit the Growth of Pancreatic Cancer by Suppressing the SCD1/BRCA1 Signaling Pathway.Molecules (Basel, Switzerland) · 2026Article
- UBA3 reduction sensitizes cancer cells to NAE inhibitors.Life science alliance · 2026Article
- RAD51 promotes osteogenic differentiation and inhibits DNA damage in osteoporosis though regulating cGAS-STING signaling pathway.Regenerative therapy · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Precision targeting of STING: Challenges, innovations, and clinical outlook for cancer therapy.Innovation (Cambridge (Mass.)) · 2026Review
- Insights into the olaparib-mediated cell death mechanisms in canine hematological malignancies: a different fate for CLBL-1 and GL-1 cell lines.Frontiers in veterinary science · 2026Article
- MCRS1 is associated with immunosuppressive microenvironments in pan-cancer and promotes hepatocellular carcinoma malignant phenotypes.Translational cancer research · 2025Article
- Review
- PARP inhibitor-induced anti-tumour chemokine response is suppressed by dipeptidyl peptidase 4 (DPP4) in ovarian cancer.British journal of cancer · 2025Article
- STAT1β modulates the tumor immune microenvironment to improve prognosis in ovarian cancer: a comprehensive study of transcriptional and protein expression differences.Journal of ovarian research · 2025Article
- CRISPR screens and quantitative proteomics reveal remodeling of the aryl hydrocarbon receptor-driven proteome through PARP7 activity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cbl-b inhibitor NX-1607 activates MAPK/ERK signaling pathway and enhances T-cell activation.Journal for immunotherapy of cancer · 2025Article
- PARP7 as a new target for activating anti-tumor immunity in cancer.EMBO molecular medicine · 2025Review
- USP7 V517F mutation as a mechanism of inhibitor resistance.Nature communications · 2025Article
- Unleashing viral mimicry: A combinatorial strategy to enhance the efficacy of PARP7 inhibitors.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA-deficient tumors. However, over 40% of BRCA-deficient patients fail to respond to PARPi. Here, we report that thioparib, a next-generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi-sensitive and -resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1-dependent DNA damage and replication stress, causing S-phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR-mediated DNA repair while increasing RAD51 foci formation. Notably, the on-target inhibition of PARP7 by thioparib-activated STING/TBK1-dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome-scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next-generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier-generation 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.