ArticleMolecular carcinogenesis2016
Inhibitors of the apurinic/apyrimidinic endonuclease 1 (APE1)/nucleophosmin (NPM1) interaction that display anti-tumor properties.
Article in Molecular carcinogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- APE1 binds and processes abasic sites present in i-motif DNA and cooperates with PCBP1 in maintenance of telomeric stability.Nucleic acids research · 2026Article
- APE1 Attenuates ALK Tyrosine Kinase Inhibitors Sensitivity in NPM1-ALK Positive Anaplastic Large Cell Lymphoma.Cancer science · 2025Article
- APE1 condensation in nucleoli of non-cancer cells depends on rRNA transcription and forming G-quadruplex RNA structures.Nucleic acids research · 2025Article
- Review
- Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.Protein and peptide letters · 2025Review
- Review
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- Genetic Influences in Cancer-Associated Myositis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Review
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- In Vitro Assay to Measure APE1 Enzymatic Activity on Ribose Monophosphate Abasic Site.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Inhibition of human APE1 and MTH1 DNA repair proteins by dextran-coated γ-FeNanomedicine (London, England) · 2022Article
- Pyroptosis: A new insight of non-small-cell lung cancer treatment.Frontiers in oncology · 2022Review
- Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy.International journal of molecular sciences · 2021Review
- Significance of NPM1 Gene Mutations in AML.International journal of molecular sciences · 2021Review
- Molecular Mechanisms Regulating the DNA Repair Protein APE1: A Focus on Its Flexible N-Terminal Tail Domain.International journal of molecular sciences · 2021Review
- Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer.Cell death & disease · 2021Article
- Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy.Frontiers in oncology · 2021Review
- The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease.Drug discovery today · 2021Review
- Evaluation of antioxidant network proteins as novel prognostic biomarkers for head and neck cancer patients.Oral oncology · 2020Article
- Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
The apurinic/apyrimidinic endonuclease 1 (APE1) is a protein central to the base excision DNA repair pathway and operates in the modulation of gene expression through redox-dependent and independent mechanisms. Aberrant expression and localization of APE1 in tumors are recurrent hallmarks of aggressiveness and resistance to therapy. We identified and characterized the molecular association between APE1 and nucleophosmin (NPM1), a multifunctional protein involved in the preservation of genome stability and rRNA maturation. This protein-protein interaction modulates subcellular localization and endonuclease activity of APE1. Moreover, we reported a correlation between APE1 and NPM1 expression levels in ovarian cancer, with NPM1 overexpression being a marker of poor prognosis. These observations suggest that tumors that display an augmented APE1/NPM1 association may exhibit increased aggressiveness and resistance. Therefore, targeting the APE1/NPM1 interaction might represent an innovative strategy for the development of anticancer drugs, as tumor cells relying on higher levels of APE1 and NPM1 for proliferation and survival may be more sensitive than untransformed cells. We set up a chemiluminescence-based high-throughput screening assay in order to find small molecules able to interfere with the APE1/NPM1 interaction. This screening led to the identification of a set of bioactive compounds that impair the APE1/NPM1 association in living cells. Interestingly, some of these molecules display anti-proliferative activity and sensitize cells to therapeutically relevant genotoxins. Given the prognostic significance of APE1 and NPM1, these compounds might prove effective in the treatment of tumors that show abundant levels of both proteins, such as ovarian or hepatic carcinomas.
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