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Fibroblast growth factor receptor alterations and resistance mechanisms in the treatment of pediatric solid tumors

Ivan Li1,2, Yuchen Huo3,2, Ting Yang4

  • 1Tufts University, Medford, MA 02155, USA.

Cancer Drug Resistance (Alhambra, Calif.)
|June 13, 2025
PubMed

Insights

Fibroblast growth factor receptor (FGFR) alterations are rare in pediatric cancers but can be targeted. Pan-FGFR inhibitor infigratinib showed promise in neuroblastoma models, suggesting therapeutic potential for pediatric FGFR-driven tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Fibroblast growth factor receptor (FGFR) family signaling is crucial for cell functions and implicated in adult cancer drug resistance.
  • FGFR alterations are targets for inhibitors in adult cancers, but their role in pediatric tumors is less understood.
  • This study investigates FGFR alterations in pediatric cancers to identify potential therapeutic targets.

Purpose of the Study:

  • To determine the prevalence and characteristics of FGFR alterations in pediatric tumors.
  • To evaluate the preclinical efficacy of a pan-FGFR inhibitor, infigratinib (BGJ398), in pediatric cancer models.
  • To provide a rationale for developing FGFR inhibitors for pediatric cancer treatment.

Main Methods:

  • Analysis of FGFR alterations across pediatric cancer databases.
  • Assessment of infigratinib's effects on pediatric cancer cell line viability, migration, and cell death using live cell imaging.
  • Evaluation of signaling pathway activity (RAS-MAPK) and apoptosis induction via Western blots.
  • Correlation of FGFR gene expression with patient outcomes in neuroblastoma.

Main Results:

  • FGFR gene alterations are rare in pediatric cancers and distinct from adult tumors.
  • FGFR1-4 overexpression, not genomic alterations, is observed in subsets of pediatric neuroblastoma and correlates with outcomes.
  • Infigratinib effectively inhibited proliferation and migration, induced cell death, and suppressed RAS-MAPK signaling in neuroblastoma cell lines.
  • Apoptosis was induced by infigratinib treatment in pediatric neuroblastoma models.

Conclusions:

  • Pediatric and adult cancers share some FGFR activation mechanisms but differ in alteration patterns.
  • FGFR overexpression in pediatric neuroblastoma suggests a potential therapeutic window for FGFR inhibitors.
  • Infigratinib demonstrates preclinical efficacy against FGFR-altered pediatric neuroblastoma, highlighting its therapeutic potential and informing resistance mechanisms.
Keywords:
FGFRneuroblastomapediatric cancerresistancetargeted therapy

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