Comprehensive multi-platform tyrosine kinase profiling reveals novel actionable FGFR aberrations across sarcomas affecting the young - PubMed
5 hours ago
- #sarcoma
- #FGFR-inhibitors
- #precision medicine
- Limited targeted agents are approved for pediatric sarcomas.
- Tyrosine kinase (TK) inhibitors show clinical efficacy in some young sarcoma patients but lack predictive response biomarkers.
- TK-activating fusions or mutations are rare in these patients, but RNA overexpression of TKs is common.
- A study of 107 sarcoma patients identified novel actionable FGFR aberrations, including a novel LSM1-FGFR1 fusion in osteosarcoma.
- High FGFR4 and FGF8 RNA expression levels indicate TK pathway activity and predict sensitivity to FGFR-inhibitors.
- FGFR4-specific inhibitor FGF401 and multi-kinase FGFR-inhibitor lenvatinib showed marked tumor growth inhibition in FP-RMS PDXs.
- A clinical response to lenvatinib was observed in a relapsed metastatic FP-RMS patient.
- The study highlights FP-rhabdomyosarcoma as a candidate for FGFR-inhibitors due to FGFR4/FGF8 co-expression.