ArticleProceedings of the National Academy of Sciences of the United States of America2019
DNA methyltransferase inhibitors induce a BRCAness phenotype that sensitizes NSCLC to PARP inhibitor and ionizing radiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 103 citations in OpenAlex.
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- Targeting the ANGPTL4/NRP1/ABL1/RAD51 axis reverses cisplatin resistance by impairing DNA damage repair in head and neck cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Altered DNA Methyltransferase Expression in Pulmonary Large-Cell Neuroendocrine Carcinoma: Pilot Experimental Data Targeted DNMT1, DNMT3A, and DNMT3B.Cancer reports (Hoboken, N.J.) · 2026Article
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- Multi-omics integration in deciphering non-small cell lung cancer drug resistance: current status, challenges, and future prospects.Hereditas · 2026Review
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- Article
- The interplay of DNA damage, epigenetics and tumour heterogeneity in driving cancer cell fitness.Nature communications · 2025Review
- Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment.bioRxiv : the preprint server for biology · 2025Article
- Article
- The Interplay Between DNA Repair and the Immune Microenvironment in Pancreatic Cancer.Biomedicines · 2025Review
- Epigenetic drugs in cancer therapy.Cancer metastasis reviews · 2025Review
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- Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.Cell communication and signaling : CCS · 2025Article
- Low dose DNA methyltransferase inhibitors potentiate PARP inhibitors in homologous recombination repair deficient tumors.Breast cancer research : BCR · 2025Article
- Review
- Review
- Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review.Translational lung cancer research · 2024Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
A minority of cancers have breast cancer gene (BRCA) mutations that confer sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis), but the role for PARPis in BRCA-proficient cancers is not well established. This suggests the need for novel combination therapies to expand the use of these drugs. Recent reports that low doses of DNA methyltransferase inhibitors (DNMTis) plus PARPis enhance PARPi efficacy in BRCA-proficient AML subtypes, breast, and ovarian cancer open up the possibility that this strategy may apply to other sporadic cancers. We identify a key mechanistic aspect of this combination therapy in nonsmall cell lung cancer (NSCLC): that the DNMTi component creates a BRCAness phenotype through downregulating expression of key homologous recombination and nonhomologous end-joining (NHEJ) genes. Importantly, from a translational perspective, the above changes in DNA repair processes allow our combinatorial PARPi and DNMTi therapy to robustly sensitize NSCLC cells to ionizing radiation in vitro and in vivo. Our combinatorial approach introduces a biomarker strategy and a potential therapy paradigm for treating BRCA-proficient cancers like NSCLC.
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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.