Fibroblast growth factor receptor 1 (FGFR1) amplification and overexpression are common events in multiple subtypes of soft tissue sarcoma, and high FGFR1-expressing soft tissue sarcoma cells are sensitive to FGFR inhibitors.1

Because high-level FGFR1 amplification was detected in a patient with metastatic leiomyosarcoma, a type of soft tissue sarcoma, researchers in Germany sought to investigate the role of FGFR1 as an oncogenic driver and potential therapeutic target in soft tissue sarcoma.

For the study, researchers assessed the frequency of FGFR1 amplification and overexpression in a cohort of 176 patients with treatment-naïve high-grade soft tissue sarcoma and validated their results using data from 256 patients included in The Cancer Genome Atlas (TCGA). They also evaluated the sensitivity of FGFR1-altered soft tissue sarcoma cells to genetic and pharmacologic FGFR1 inhibition.

Results showed FGFR1 amplification and overexpression were present in 31% and 34% of cases in the 176 untreated patients with high-grade soft tissue sarcoma and in 16% and 15% of cases in the TCGA cohort, respectively. Of note, researchers detected FGFR1 overexpression without amplification in a substantial proportion of cases.

Furthermore, researchers found that high FGFR1-expressing soft tissue sarcoma cells were sensitive to FGFR inhibition by inhibitors that include PD173074, AZD4547, and BGJ398. The study demonstrated that the degree of dependence on FGFR1 for proliferation, survival, and growth was primary influenced by FGFR1 expression levels.

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These findings ultimately supported FGFR1 as a novel therapeutic target in soft tissue sarcoma and suggested that FGFR1 overexpression was a more reliable biomarker of sensitivity to FGFR pathway inhibition compared with genomic amplification.

Reference

  1. Chudasama P, Renner M, Specht K, et al. FGFR1 overexpression is frequent in adult soft tissue sarcoma and predicts sensitivity to FGFR inhibitors. Poster presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.