ArticleBritish journal of cancer2022
Fibroblast growth factor signalling influences homologous recombination-mediated DNA damage repair to promote drug resistance in ovarian cancer.
Article in British journal of cancer, 2022. 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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17 citing papers in PubMed, 23 citations in OpenAlex.
- The ARTEMIS trial identifies immune activation as a key predictor of neoadjuvant chemotherapy response in triple-negative breast cancer.Breast cancer research : BCR · 2026Trial
- The role of cytokines in ovarian cancer drug resistance.International journal of cancer · 2026Review
- Engineering immune-competent niches: strategies, applications, and translational hurdles in ovarian cancer organoid models.Frontiers in immunology · 2026Review
- Repurposing the Tyrosine Kinase Inhibitors Targeting FGFR and VEGFR Pathways for Cancer Therapy: A Comprehensive Review.Cancers · 2025Review
- FGFR inhibition as a new therapeutic strategy to sensitize glioblastoma stem cells to tumor treating fields.Cell death discovery · 2025Article
- Efficacy of lenvatinib combined with TAS-102 as second-line therapy for advanced intrahepatic cholangiocarcinoma: a case report.Frontiers in oncology · 2025Article
- FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases.Cellular and molecular life sciences : CMLS · 2024Article
- Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization ofCells · 2024Article
- Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation.Cancer metastasis reviews · 2024Review
- Radiation exposure lymphocyte damage assessed by γ-H2AX level using flow cytometry.Scientific reports · 2024Article
- NPAS2 dampens chemo-sensitivity of lung adenocarcinoma cells by enhancing DNA damage repair.Cell death & disease · 2024Article
- Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.International journal of biological sciences · 2024Article
- Fanconi anemia associated protein 20 (FAAP20) plays an essential role in homology-directed repair of DNA double-strand breaks.Communications biology · 2023Article
- Microsatellite instability states serve as predictive biomarkers for tumors chemotherapy sensitivity.iScience · 2023Article
- Autocrine EGF and TGF-α promote primary and acquired resistance to ALK/c-Met kinase inhibitors in non-small-cell lung cancer.Pharmacology research & perspectives · 2023Article
- Metabolic reprogramming of three major nutrients in platinum-resistant ovarian cancer.Frontiers in oncology · 2023Review
- Role of epithelial-mesenchymal transition factor SNAI1 and its targets in ovarian cancer aggressiveness.Journal of cancer metastasis and treatment · 2023Article
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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
backgroundOvarian cancer patients frequently develop chemotherapy resistance, limiting treatment options. We have previously shown that individuality in fibroblast growth factor 1 (FGF1) expression influences survival and chemotherapy response.
methodsWe used MTT assays to assess chemosensitivity to cisplatin and carboplatin following shRNA-mediated knockdown or heterologous over-expression of FGF1 (quantified by qRT-PCR and immunoblot analysis), and in combination with the FGFR inhibitors AZD4547 and SU5402, the ATM inhibitor KU55933 and DNA-PK inhibitor NU7026. Immunofluorescence microscopy was used to quantify the FGF1-dependent timecourse of replication protein A (RPA) and γH2AX foci formation.
resultsPharmacological inhibition of FGF signalling reversed drug resistance in immortalised cell lines and in primary cell lines from drug-resistant ovarian cancer patients, while FGF1 over-expression induced resistance. Ataxia telangiectasia mutated (ATM) phosphorylation, but not DNA adduct formation was FGF1 dependent, following cisplatin or carboplatin challenge. Combining platinum drugs with the ATM inhibitor KU55933, but not with the DNA-PK inhibitor NU7026 re-sensitised resistant cells. FGF1 expression influenced the timecourse of damage-induced RPA and γH2AX nuclear foci formation.
conclusionDrug resistance arises from FGF1-mediated differential activation of high-fidelity homologous recombination DNA damage repair. FGFR and ATM inhibitors reverse platinum drug resistance, highlighting novel combination chemotherapy approaches for future clinical trial evaluation.
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