The fibroblast growth factor receptor type
1 gene (FGFR1) encodes one member of the
FGFR tyrosine kinase (TK) family, which
includes four kinases: FGFR1, 2, 3, and 4
(Figure 1). FGFR TKs play crucial roles in development and have been shown in cancers to be
deregulated by either amplification, point mutation,
or translocation (Turner
and Grose 2010). Amplification or activation of FGFR1 has been reported in many
cancers including oral squamous cell carcinoma (Freier et al.
2007), breast cancer (Turner et al. 2010), esophageal
squamous cell carcinoma (Ishizuka et al. 2002), ovarian cancer (Gorringe et al.
2007), bladder cancer (Simon et al. 2001), prostate cancer
(Edwards et al.
2003), and lung cancer, predominantly in the squamous subtype (Dutt et al.
et al. 2007; Weiss et al. 2010).
Figure 1. Schematic of FGFR signaling pathway. Growth factor binding to
FGFR results in activation of the MAPK signaling pathway
(RAS-RAF-MEK-ERK). The letter "K" within the schema denotes the tyrosine kinase domain.
Suggested Citation: Sos, M., R. Thomas. 2015. FGFR1. My Cancer Genome
(Updated December 7).
Last Updated: December 7, 2015
FGFR1 in NSCLC
Amplifications of FGFR1 are predominantly found in squamous cell lung cancers from
former/current smokers. The chromosomal region at 8p12 spanning the FGFR1 gene locus is amplified in up to ~20% of
squamous cell lung cancer patients. Copy number
changes can be detected by various techniques, including fluorescence in situ
hybridization (FISH) analysis (Dutt et al. 2011; Turner and Seckl 2010;
Weiss et al. 2010);
the exact clinically relevant cutoff levels for amplification remain to be determined. In
lung cancer patients with other histologies such as adenocarcinoma, FGFR1
amplification is a rare event (less than 2%; Dutt et al.
and Seckl 2010; Weiss et al. 2010). Preclinical data
suggest that cancer cells with amplified FGFR1 can display "addiction" to FGFR
Suggested Citation: Sos, M., R. Thomas. 2015. FGFR1 in NSCLC. My Cancer
(Updated June 18).
Last Updated: June 18, 2015
FGFR1 Amplification in SCC of the Lung
a Tumor cells with FGFR1 amplification are dependent on the activity of the
receptor. This dependency can be exploited
therapeutically with specific FGFR inhibitors that show promising activity in preclinical
models of lung cancer (Dutt et al. 2011; Weiss et al. 2010).
A pan-FGFR TKI has been shown to block tumor proliferation and induce apoptosis in a subset
of NSCLC cell lines with activated FGFR signaling but has no effect on cells that do not
activate the pathway (Marek
et al. 2009; Weiss et al. 2010). Clinical trials
with FGFR inhibitors are currently underway.
Suggested Citation: Sos, M., R. Thomas. 2012. FGFR1 Amplification in SCC of the
Lung. My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/fgfr1/58/
(Updated November 15).
Last Updated: November 15, 2012
My Cancer Genome has released its new and improved cancer clinical trials search tool on our
beta website. Please visit beta.padiracinnovation.org
to check it out!