Preclinical Evaluation of the FGFR-Family Inhibitor Futibatinib for Pediatric Rhabdomyosarcoma

Jerry T. Wu, Adam Cheuk, Kristine Isanogle, Christina Robinson, Xiaohu Zhang, Michele Ceribelli, Erin Beck, Paul Shinn, Carleen Klumpp-Thomas, Kelli M. Wilson, Crystal McKnight, Zina Itkin, Hiroshi Sotome, Hiroshi Hirai, Elizabeth Calleja, Volker Wacheck, Brad Gouker, Cody J. Peer, Natalia Corvalan, David MilewskiYong Y. Kim, William D. Figg, Elijah F. Edmondson, Craig J. Thomas, Simone Difilippantonio, Jun S. Wei, Javed Khan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. Despite decades of clinical trials, the overall survival rate for patients with relapsed and metastatic disease remains below 30%, underscoring the need for novel treatments. FGFR4, a receptor tyrosine kinase that is overexpressed in RMS and mutationally activated in 10% of cases, is a promising target for treatment. Here, we show that futibatinib, an irreversible pan-FGFR inhibitor, inhibits the growth of RMS cell lines in vitro by inhibiting phosphorylation of FGFR4 and its downstream targets. Moreover, we provide evidence that the combination of futibatinib with currently used chemotherapies such as irinotecan and vincristine has a synergistic effect against RMS in vitro. However, in RMS xenograft models, futibatinib monotherapy and combination treatment have limited efficacy in delaying tumor growth and prolonging survival. Moreover, limited efficacy is only observed in a PAX3-FOXO1 fusion-negative (FN) RMS cell line with mutationally activated FGFR4, whereas little or no efficacy is observed in PAX3-FOXO1 fusion-positive (FP) RMS cell lines with FGFR4 overexpression. Alternative treatment modalities such as combining futibatinib with other kinase inhibitors or targeting FGFR4 with CAR T cells or antibody-drug conjugate may be more effective than the approaches tested in this study.

Original languageEnglish
Article number4034
Issue number16
StatePublished - Aug 2023
Externally publishedYes


  • FGFR inhibitor
  • FGFR4
  • futibatinib
  • pediatric cancer
  • rhabdomyosarcoma


Dive into the research topics of 'Preclinical Evaluation of the FGFR-Family Inhibitor Futibatinib for Pediatric Rhabdomyosarcoma'. Together they form a unique fingerprint.

Cite this