title: Therapeutic targeting of fibroblast growth factor receptors in gastric cancer.
abstract: Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 (HER2) have become standard therapy for HER2-positive GC. An inhibitor of vascular endothelial growth factor receptor 2 or MET has also produced promising results in patients with GC. Fibroblast growth factor receptors (FGFR) play key roles in tumor growth via activated signaling pathways in GC. Genomic amplification of FGFR2 leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical relevance of FGFR in GC and examines FGFR as a potential therapeutic target in patients with GC. Preclinical studies in animal models suggest that multitargeted tyrosine kinase inhibitors (TKIs), including FGFR inhibitor, suppress tumor cell proliferation and delay tumor progression. Several TKIs are now being evaluated in clinical trials as treatment for metastatic or unresectable GC harboring FGFR2 amplification.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Mikito
authors.identifier: 0000-0001-7321-848X
authors.initials: M
authors.lastname: Inokuchi
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujimori
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Otsuki
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Minimally Invasive Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Kazuyuki
authors.identifier: 0000-0003-1039-1749
authors.initials: K
authors.lastname: Kojima