Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Feb;12(2):107-23.
doi: 10.2174/156800912799095144.

Adding to the mix: fibroblast growth factor and platelet-derived growth factor receptor pathways as targets in non-small cell lung cancer

S A Kono  1 , L E Heasley, R C Doebele, D R Camidge
Affiliations
Review

Adding to the mix: fibroblast growth factor and platelet-derived growth factor receptor pathways as targets in non-small cell lung cancer

S A Kono et al. Curr Cancer Drug Targets. 2012 Feb.

Abstract

The treatment of advanced non � small cell lung cancer (NSCLC) increasingly involves the use of molecularly targeted therapy with activity against either the tumor directly, or indirectly, through activity against host-derived mechanisms of tumor support such as angiogenesis. The most well studied signaling pathway associated with angiogenesis is the vascular endothelial growth factor (VEGF) pathway, and the only antiangiogenic agent currently approved for the treatment of NSCLC is bevacizumab, an antibody targeted against VEGF. More recently, preclinical data supporting the role of fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR) signaling in angiogenesis have been reported. The platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) pathways may also stimulate tumor growth directly through activation of downstream mitogenic signaling cascades. In addition, 1 or both of these pathways have been associated with resistance to agents targeting the epidermal growth factor receptor (EGFR) and VEGF. A number of agents that target FGF and/or PDGF signaling are now in development for the treatment of NSCLC. This review will summarize the potential molecular roles of PDGFR and FGFR in tumor growth and angiogenesis, as well as discuss the current clinical status of PDGFR and FGFR inhibitors in clinical development.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest Drs Kono, Heasley, Doebele, and Camidge have no potential conflicts of interest to disclose.

Figures

Figure 1
Figure 1. Schematic of the potential roles of the FGFR and PDGFR pathways in tumor proliferation and angiogenesis
Autocrine and paracrine signaling of the FGF and PDGF pathways may contribute to tumor proliferation (A) and angiogenesis (B). (A) Activation of FGFR and PDGFR from ligands expressed by tumor cells or other tissues results in stimulation of mitogenic downstream cascades. (B) Similarly, PDGF secreted from endothelial cells may recruit pericytes necessary for angiogenesis through paracrine signaling. In addition, activation of FGFR on endothelial cells results in cellular proliferation and increased angiogenesis. FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; PDGF, platelet-derived growth factor; PDGFR, platelet-derived growth factor receptor.
Figure 2
Figure 2. Molecular targets of the investigational multitargeted TKIs being studied in NSCLC and PDGFR- and FGFR-specific agents in earlier clinical development
Illustration depicting targeted inhibition of the VEGF, PDGF, and FGF pathways by monoclonal antibodies and TKIs. FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; PDGF, platelet-derived growth factor; PDGFR, platelet-derived growth factor receptor; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. American Cancer Society. Cancer Facts & Figures, 2010. American Cancer Society; Atlanta, GA: 2010.
    1. Surveillance Epidemiology and End Results; National Cancer Institute. [Accessed April 30, 2010];SEER Stat Fact Sheets: Lung and Bronchus. 2010 http://seer.cancer.gov/statfacts/html/lungb.html.
    1. Sequist LV, Bell DW, Lynch TJ, Haber DA. Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol. 2007;25(5):587–595. - PubMed
    1. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–957. - PubMed
    1. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7(3):169–181. - PubMed

Publication types

MeSH terms

Substances