• What is FGFR1?
  • FGFR1 in Breast Cancer
  • FGFR1 Amplification
  • Clinical Trials

FGFR1

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. 2011Weir et al. 2007Weiss et al. 2010).

fgfr1.png

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.

Related Pathways

Contributors: Martin Sos, M.D., Roman K. Thomas, M.D.

Suggested Citation: Sos, M., R. Thomas. 2015. FGFR1. My Cancer Genome https://www.padiracinnovation.org/content/disease/breast-cancer/fgfr1/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

FGFR1 in Breast Cancer

The chromosomal region at 8p11–12 containing the FGFR1 gene locus is amplified in up to 10% of breast cancer patients (Hynes and Dey 2010). Turner et al. (2010) noted that FGFR1 overexpression has been associated with ER-positive status and luminal B–type breast cancer. 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. Preclinical data suggest that cancer cells with amplified FGFR1 can display "addiction" to FGFR signaling.


Gene Invasive Breast Cancer Hormone Receptor Positive (ER+ and/or PR+) Invasive Breast Cancer HER2 Positive Invasive Breast Cancer Triple-Negative Invasive Breast Cancer
FGFR1a 10-13% (Courjal et al. 1997; Gelsi-Boyer et al. 2005; Jacquesmier et al. 1994; Jain and Turner 2012​; Letessier et al. 2006; Reis-Filho et al. 2006; TCGA-cBio) 8.6% (Elbauomy Elsheikh et al. 2007)
14.3% (TCGA-cBio)
7.7% (Elbauomy Elsheikh et al. 2007)
11.7% (TCGA-cBio)
5.5% (Elbauomy Elsheikh et al. 2007)
13.4% (TCGA-cBio)

a Data from Courjal et al. (1997) were measured using Southern blot analysis. Data from Elbauomy Elsheikh et al. (2007) were measured using chromogenic in situ hybridization (CISH). Data from Gelsi-Boyer et al. (2005) were measured using fluorescence in situ hybridization (FISH). Data from Jacquesmier et al. (1994) were measured using Southern and Northern blot analysis. Data from Letessier et al. (2006) were measured using FISH. Data from Reis-Filho et al. (2006) were measured using CISH and FISH. Data from TCGA-cBio were measured using next-generation sequencing (NGS).

Contributors: Justin M. Balko, Pharm. D., Ph.D., Ingrid A. Mayer, M.D., M.S.C.I., Mia Levy, M.D., Ph.D., Nicholas Turner, M.D., Ph.D., Carlos L. Arteaga, M.D.

Suggested Citation: Balko, J., I. Mayer, M. Levy, N. Turner, C. Arteaga. 2013. FGFR1 in Breast Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/breast-cancer/fgfr1/ (Updated October 1).

Last Updated: October 1, 2013

FGFR1 Amplification in Breast Cancer

Properties
Location of mutation Not applicable
Frequency of FGFR1 amplification in breast cancer 10-13% (Courjal et al. 1997; Gelsi-Boyer et al. 2005; Jacquesmier et al. 1994; Jain and Turner 2012; Letessier et al. 2006; Reis-Filho et al. 2006; TCGA-cBio)
Implications for Targeted Therapeutics
Response to FGFR inhibitors Unknown at this timea
Response to endocrine therapy Unknown at this timeb

a Tumor cells with FGFR1 amplification depend on the activity of the receptor. This dependency can be exploited therapeutically with specific FGFR1 inhibitors that show activity in preclinical models of breast cancer (Gozgit et al. 2012; Shiang et al. 2010). Pan-FGFR TKIs have been shown to reduce cell growth in breast cancer cell lines with activated FGFR signaling, but the same drugs had little to no effect on cells without the activated pathway (Gozgit et al. 2012; Shiang et al. 2010). Clinical trials with FGFR inhibitors are currently underway.

b Turner et al. (2010) showed in preclinical studies that FGFR1 amplification promoted resistance to endocrine therapies.

Contributors: Justin M. Balko, Pharm. D., Ph.D., Ingrid A. Mayer, M.D., M.S.C.I., Mia Levy, M.D., Ph.D., Nicholas Turner, M.D., Ph.D., Carlos L. Arteaga, M.D.

Suggested Citation: Balko, J., I. Mayer, M. Levy, N. Turner, C. Arteaga. 2013. FGFR1 Amplification in Breast Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/breast-cancer/fgfr1/58/ (Updated October 1).

Last Updated: October 1, 2013

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