FGF-trapping hampers cancer stem-like cells in uveal melanoma

Alessandra Loda, Stefano Calza, Arianna Giacomini, Cosetta Ravelli, Adwaid Manu Krishna Chandran, Chiara Tobia, Giovanna Tabellini, Silvia Parolini, Francesco Semeraro, Roberto Ronca, Sara Rezzola

Research output: Contribution to journalArticlepeer-review


Background: Cancer 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. Methods: Herein, 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. Results: By 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. Conclusions: Our 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.

Original languageEnglish (US)
Article number89
Pages (from-to)89
JournalCancer Cell International
Issue number1
StatePublished - May 11 2023


  • Cancer stem-like cells
  • FGF
  • FGF inhibitor
  • Uveal melanoma

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research


Dive into the research topics of 'FGF-trapping hampers cancer stem-like cells in uveal melanoma'. Together they form a unique fingerprint.

Cite this