Fibroblast growth factor receptor signaling as therapeutic targets in gastric cancer

Table 1 Recent preclinical studies of flobrast growth factor receptor-targeted therapy in gastric cancer

FGFRs targeted therapeutics (Campany)	Study (Ref.)	Main results
Multikinase inhibitors
Ki23057 (KIRIN Brewery)	Nakamura et al[42]	Ki23057 significantly inhibited the proliferation and induced apoptosis in scirrhous gastric cancer lines
Dovitinib (Novartis)	Deng et al[20]	Dovitinib specifically inhibited cell proliferation and induced apoptosis in gastric cancer cells with potent amplification of FGFR1
S49076	Burbridge et al[43]	S49076 impaired the growth of MET- and FGFR2-dependent gastric cancer cells and showed good synergistic inhibition of MET and FGFR2 in vivo medel
Foretinib (GlaxoSmithKline)	Kataoka et al[47]	Foretinib inhibits the cell growth of gastric cancer cell lines by inhibiting not only MET but also FGFR kinase
FGFRs specific inhibitors
AZD4547 (AstraZeneca)	Xie et al[50]	AZD4547 application resulted in tumor growth inhibition in FGFR2-amplified gastric tumor xenograft and induction of apoptosis by impairing downstream signaling of FGFR2
PD173074	Kunii et al[23]	FGFR2 inhibition by PD173074 displayed potent and selective growth inhibition in FGFR2-amplified gastric cancer cell lines
LY2874455 (Eli Lilly and Company)	Zhao et al[51]	LY2874455 is more potent at inhibiting the growth of gastric cancer cells with an increased FGFRs-signaling activity without high blood pressure
RNA based therapy
siRNA	Zhou et al[54]	Treatment with siRNA resulted in reduced proliferation and prompted apoptosis, which accompanied the reduction of VEGFR expression and increase of apoptosis-related proteins
miR-133b	Wen et al[55]	Some micro RNAs (miR-133b) may contribute to the regulation of FGFR-1 receptor in gastric carcinomas such that FGFR1 expression is inversely correlated with miR- 133b expression
FGFRs antibodies
Gal-FR21, 22 and 23	Zhao et al[52]	Highly specific monoclonal antibodies against FGFR2 strongly depressed growth of xenografts from 2 gastric cancer cell lines, OCUM-2M and SNU-16
GP369	Bai et al[53]	GP369, an FGFR2-IIIb-specificantibody, exhibited anti-proliferative activity against gastric cancers driven FGFR2 overexpression

FGFR: Flobrast growth factor receptor; VEGFR: Vascular endothelial growth factor receptor.

Table 2 Clinical trials of fiblobrast growth factor receptor 2-targeted therapy in gastric cancer

Trial	Study design	FGFRs status	Regimen	Response rate	Status
NCT01457846	Phase I/1st	FGFR2amplification FISH +	AZD4547	38.5% (contained SD)	Conducted
SHINE	Phase II/1st	FGFR2amplification FISH +	AZD4547 paclitaxel		Computed accural
NCT01719549	Phase II/2nd	FGFR2 amplification	Dovitinib		Ongoing
NCT01921673	Phase I/II/2nd	FGFR2 amplification	Dovitinib, docetaxel		Ongoing
NCT02052778	Phase I/II/2nd	FGF/FGFR-Related Abnormalities	TAS-120		Ongoing
NCT02318329	Phase I/1st	FGFR2b overexpression and FGFR2 amplification	FPA144		Ongoing

FGFR: Fiblobrast growth factor receptor; FISH: Fluorescence in situ hybridization; SD: Stable disease.