ArticleCancer cell international2023
FGF-trapping hampers cancer stem-like cells in uveal melanoma.
Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 6 citations in OpenAlex.
- Identification and Validation of an E2F Targets-Related Gene Signature Risk Score Predicting the Prognosis of Patients with Uveal Melanoma.Ocular oncology and pathology · 2026Article
- Extracellular Matrix Stiffness Regulates Cancer Stemness in Uveal Melanoma via the PIEZO1-DOT1L Axis.Investigative ophthalmology & visual science · 2025Article
- Targeting CERS6-AS1/FGFR1 axis as synthetic vulnerability to constrain stromal cells supported proliferation in Mantle cell lymphoma.Leukemia · 2024Article
- Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells.Experimental hematology & oncology · 2024Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCancer stem-like cells (CSCs) are a subpopulation of tumor cells responsible for tumor initiation, metastasis, chemoresistance, and relapse. Recently, CSCs have been identified in Uveal Melanoma (UM), which represents the most common primary tumor of the eye. UM is highly resistant to systemic chemotherapy and effective therapies aimed at improving overall survival of patients are eagerly required.
methodsHerein, taking advantage from a pan Fibroblast Growth Factor (FGF)-trap molecule, we singled out and analyzed a UM-CSC subset with marked stem-like properties. A hierarchical clustering of gene expression data publicly available on The Cancer Genome Atlas (TCGA) was performed to identify patients' clusters.
resultsBy disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity. Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth. At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes.
conclusionsOur findings support the evidence that the FGF/FGFR axis represents a master regulator of cancer stemness in primary UM tumors and point to anti-FGF treatments as a novel therapeutic strategy to hit the CSC component in UM.
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