FGFR3–TACC3: A novel gene fusion in cervical cancer

•The first cases of cervical carcinoma harboring an FGFR3–TACC3 fusion•One of patients whose tumor contained the FGFR3–TACC3 fusion received an investigational FGFR tyrosine kinase inhibitor•Manuscript highlights the role of genomic profiling identifying new therapeutic targets and targeted therapies

Cervical cancer epitomizes the success of cancer prevention through the human papillomavirus (HPV) vaccine, but significant challenges remain in the treatment of advanced disease. We report the first three cases of cervical carcinoma harboring an FGFR3–TACC3 fusion, which serves as a novel therapeutic target. The fusion, identified by comprehensive genomic profiling, activates the FGFR pathway that has been implicated in HPV-driven carcinogenesis. One of the patients whose tumor contained the FGFR3–TACC3 fusion was treated with an investigational FGFR tyrosine kinase inhibitor. Concomitant molecular alterations involving the PI3K/AKT/mTOR and RAF/MEK pathways were also identified and suggest other treatment strategies that deserve investigation. This case series highlights the role of comprehensive genomic profiling in the identification of new therapeutic targets and in targeted therapy selection for patients with cervical cancer.