ArticleMolecular cancer2010
Down-regulation of the nucleotide excision repair gene XPG as a new mechanism of drug resistance in human and murine cancer cells.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.Nutrition & metabolism · 2026Review
- Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment.Molecules (Basel, Switzerland) · 2023Review
- XPG in the Nucleotide Excision Repair and Beyond: a study on the different functional aspects of XPG and its associated diseases.Molecular biology reports · 2022Review
- Mechanism-based design of agents that selectively target drug-resistant glioma.Science (New York, N.Y.) · 2022Article
- Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment.International journal of molecular sciences · 2021Review
- Role of Nucleotide Excision Repair in Cisplatin Resistance.International journal of molecular sciences · 2020Review
- Epigenetic based synthetic lethal strategies in human cancers.Biomarker research · 2020Review
- Epigenetic heterogeneity in cancer.Biomarker research · 2019Review
- Molecular Recognition of Parallel G-quadruplex [d-(TTGGGGT)]₄ ContainingMolecules (Basel, Switzerland) · 2018Article
- Platinum sensitivity and DNA repair in a recently established panel of patient-derived ovarian carcinoma xenografts.Oncotarget · 2018Article
- The clinical value of aberrant epigenetic changes of DNA damage repair genes in human cancer.Oncotarget · 2016Review
- Expression of XPG protein in the development, progression and prognosis of gastric cancer.PloS one · 2014Article
- DNA-damage response gene polymorphisms and therapeutic outcomes in ovarian cancer.The pharmacogenomics journal · 2013Article
- Expression of XPG protein in human normal and tumor tissues.International journal of clinical and experimental pathology · 2013Article
- DNA methylation profiling in the clinic: applications and challenges.Nature reviews. Genetics · 2012Review
- Article
- MicroRNA gene dosage alterations and drug response in lung cancer.Journal of biomedicine & biotechnology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDrug resistance is one of the major obstacles limiting the activity of anticancer agents. Activation of DNA repair mechanism often accounts for increase resistance to cancer chemotherapy.
resultsWe present evidence that nemorubicin, a doxorubicin derivative currently in clinical evaluation, acts through a mechanism of action different from classical anthracyclines, requiring an intact nucleotide excision repair (NER) system to exert its activity. Cells made resistant to nemorubicin show increased sensitivity to UV damage. We have analysed the mechanism of resistance and discovered a previously unknown mechanism resulting from methylation-dependent silencing of the XPG gene. Restoration of NER activity through XPG gene transfer or treatment with demethylating agents restored sensitivity to nemorubicin. Furthermore, we found that a significant proportion of ovarian tumors present methylation of the XPG promoter.
conclusionsMethylation of a NER gene, as described here, is a completely new mechanism of drug resistance and this is the first evidence that XPG gene expression can be influenced by an epigenetic mechanism. The reported methylation of XPG gene could be an important determinant of the response to platinum based therapy. In addition, the mechanism of resistance reported opens up the possibility of reverting the resistant phenotype using combinations with demethylating agents, molecules already employed in the clinical setting.
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