ABSTRACT
Sinonasal squamous cell carcinomas (SNSCCs) are uncommon and they are associated with adverse prognosis. HPV-associated SNSCCs and fusion-driven SNSCCs are particularly rare. A case of an HPV-associated SNSCC with a FGFR3::TACC3 fusion is thus presented; a brief review of the pertinent literature is also provided.
Subject(s)
Carcinoma, Squamous Cell , Receptor, Fibroblast Growth Factor, Type 3 , Humans , Receptor, Fibroblast Growth Factor, Type 3/genetics , Carcinoma, Squamous Cell/virology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Microtubule-Associated Proteins/genetics , Male , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Paranasal Sinus Neoplasms/virology , Paranasal Sinus Neoplasms/pathology , Paranasal Sinus Neoplasms/genetics , Middle Aged , FemaleSubject(s)
Adenocarcinoma/genetics , Circulating Tumor DNA/analysis , Lung Neoplasms/genetics , Microtubule-Associated Proteins/genetics , Oncogene Proteins, Fusion/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Adenocarcinoma/drug therapy , Afatinib , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung , Cetuximab/therapeutic use , Drug Resistance, Neoplasm/genetics , ErbB Receptors/genetics , Female , Gene Expression Profiling , Genome/genetics , Humans , Lung Neoplasms/drug therapy , Mutation/genetics , Neoplasm Metastasis , Quinazolines/therapeutic use , RecurrenceABSTRACT
FGF/FGFR gene aberrations such as amplification, mutation and fusion are associated with many types of human cancers including urothelial cancer. FGFR kinase inhibitors are expected to be a targeted therapy for urothelial cancer harboring FGFR3 gene alternations. ASP5878, a selective inhibitor of FGFR1, 2, 3 and 4 under clinical investigation, selectively inhibited cell proliferation of urothelial cancer cell lines harboring FGFR3 point mutation or fusion (UM-UC-14, RT-112, RT4 and SW 780) among 23 urothelial cancer cell lines. Furthermore, ASP5878 inhibited cell proliferation of adriamycin-resistant UM-UC-14 cell line harboring MDR1 overexpression and gemcitabine-resistant RT-112 cell line. The protein expression of c-MYC, an oncoprotein, in gemcitabine-resistant RT-112 cell line was higher than that in RT-112 parental cell line and ASP5878 decreased the c-MYC expression in both RT-112 parental and gemcitabine-resistant RT-112 cell lines. Once-daily oral administration of ASP5878 exerted potent antitumor activities in UM-UC-14, RT-112 and gemcitabine-resistant RT-112 xenograft models without affecting body weight. These findings suggest that ASP5878 has the potential to be an oral targeted therapy against urothelial cancer harboring FGFR3 fusion or FGFR3 point mutation after the acquisition of gemcitabine- or adriamycin-resistance.