ArticleProceedings of the National Academy of Sciences of the United States of America2020
Pharmacologic induction of innate immune signaling directly drives homologous recombination deficiency.
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 31 papers.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
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- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- Analysis of the NLRP3 inflammasome components expression in triple-negative breast cancer patients with and without BRCA1 mutations.Scientific reports · 2026Article
- Beyond tumour suppression: cGAS-STING pathway in urologic malignancies: Context-dependent duality and therapeutic implications.Clinical and translational medicine · 2025Review
- The Interplay Between DNA Repair and the Immune Microenvironment in Pancreatic Cancer.Biomedicines · 2025Review
- ZNFX1 Functions as a Master Regulator of Epigenetically Induced Pathogen Mimicry and Inflammasome Signaling in Cancer.Cancer research · 2025Article
- ZNFX1 is a Novel Master Regulator in Epigenetically-induced Pathogen Mimicry and Inflammasome Signaling in Cancer.bioRxiv : the preprint server for biology · 2024Article
- Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.Molecular cancer therapeutics · 2024Article
- Zebularine potentiates anti-tumor immunity by inducing tumor immunogenicity and improving antigen processing through cGAS-STING pathway.Communications biology · 2024Article
- Tracing back primed resistance in cancer via sister cells.Nature communications · 2024Article
- SETD2 Deficiency Confers Sensitivity to Dual Inhibition of DNA Methylation and PARP in Kidney Cancer.Cancer research · 2023Article
- Induction of pyroptotic cell death as a potential tool for cancer treatment.Journal of inflammation (London, England) · 2022Review
- Review
- The STING pathway: Therapeutic vulnerabilities in ovarian cancer.British journal of cancer · 2022Review
- Bioinformatics: From NGS Data to Biological Complexity in Variant Detection and Oncological Clinical Practice.Biomedicines · 2022Review
- Inhibiting DNA methylation improves antitumor immunity in ovarian cancer.The Journal of clinical investigation · 2022Article
- Activating STING1-dependent immune signaling inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Recurrent transcriptional responses in AML and MDS patients treated with decitabine.Experimental hematology · 2022Article
- The epigenetics of breast cancer - Opportunities for diagnostics, risk stratification and therapy.Epigenetics · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Poly(ADP ribose) polymerase inhibitors (PARPi) have efficacy in triple negative breast (TNBC) and ovarian cancers (OCs) harboring BRCA mutations, generating homologous recombination deficiencies (HRDs). DNA methyltransferase inhibitors (DNMTi) increase PARP trapping and reprogram the DNA damage response to generate HRD, sensitizing BRCA-proficient cancers to PARPi. We now define the mechanisms through which HRD is induced in BRCA-proficient TNBC and OC. DNMTi in combination with PARPi up-regulate broad innate immune and inflammasome-like signaling events, driven in part by stimulator of interferon genes (STING), to unexpectedly directly generate HRD. This inverse relationship between inflammation and DNA repair is critical, not only for the induced phenotype, but also appears as a widespread occurrence in The Cancer Genome Atlas datasets and cancer subtypes. These discerned interactions between inflammation signaling and DNA repair mechanisms now elucidate how epigenetic therapy enhances PARPi efficacy in the setting of BRCA-proficient cancer. This paradigm will be tested in a phase I/II TNBC clinical trial.
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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.