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Fibroblast growth factor receptor 4 (FGFR4) is known to contribute to rhabdomyosarcoma progression; here, we sought to investigate the involvement and potential for therapeutic targeting of other FGFRs in this disease. Cell\u2010based screening of FGFR inhibitors with potential for clinical repurposing (NVP\u2010BGJ398, nintedanib, dovitinib, and ponatinib) revealed greater sensitivity of fusion\u2010gene\u2010positive versus fusion\u2010gene\u2010negative rhabdomyosarcoma cell lines and was shown to be correlated with high expression of FGFR2 and its specific ligand, FGF7. Furthermore, patient samples exhibit higher mRNA levels of\n                    <jats:italic>FGFR2<\/jats:italic>\n                    and\n                    <jats:italic>FGF7<\/jats:italic>\n                    in fusion\u2010gene\u2010positive versus fusion\u2010gene\u2010negative rhabdomyosarcomas. Sustained intracellular mitogen\u2010activated protein kinase (MAPK) activity and FGF7 secretion into culture media during serum starvation of\n                    <jats:italic>PAX3\u2013FOXO1<\/jats:italic>\n                    rhabdomyosarcoma cells together with decreased cell viability after genetic silencing of\n                    <jats:italic>FGFR2<\/jats:italic>\n                    or\n                    <jats:italic>FGF7<\/jats:italic>\n                    was in keeping with a novel FGF7\u2013FGFR2 autocrine loop. FGFR inhibition with NVP\u2010BGJ398 reduced viability and was synergistic with SN38, the active metabolite of irinotecan.\n                    <jats:italic>In\u2009vivo<\/jats:italic>\n                    , NVP\u2010BGJ398 abrogated xenograft growth and warrants further investigation in combination with irinotecan as a therapeutic strategy for fusion\u2010gene\u2010positive rhabdomyosarcomas.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13145","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T21:49:50Z","timestamp":1638308990000},"page":"1272-1289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["FGF7\u2013FGFR2 autocrine signaling increases growth and chemoresistance of fusion\u2010positive rhabdomyosarcomas"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1744-6071","authenticated-orcid":false,"given":"Christopher I.","family":"Milton","sequence":"first","affiliation":[{"name":"Sarcoma Molecular Pathology Team Divisions of Molecular Pathology and Cancer Therapeutics The Institute of Cancer Research London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Selfe","sequence":"additional","affiliation":[{"name":"Sarcoma Molecular Pathology Team Divisions of Molecular Pathology and Cancer Therapeutics The Institute of Cancer Research London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Aladowicz","sequence":"additional","affiliation":[{"name":"Sarcoma Molecular Pathology Team Divisions of Molecular Pathology and Cancer Therapeutics The Institute of Cancer Research London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella Y. 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