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Curr Cancer Drug Targets. 2012 Feb;12(2):107-23.

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

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  • 1Aerodigestive and Thoracic Tumor Program, Winship Cancer Institute, Emory University, Room C3005, 1365 Clifton Road NE, Atlanta, GA 30322, USA. skono@emory.edu

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.

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ClinicalTrials.gov NCT00816400 NCT00265317 NCT00003775 NCT00913835 NCT01213160 NCT01204710 NCT00609804 NCT00581789 NCT00866528 NCT00064350 NCT00600015 NCT01268566 NCT00754923 NCT01185964 NCT00979134 NCT00555256 NCT01225302 NCT00369070 NCT01313663 NCT00533585 NCT00870532 NCT01202591 NCT00454194 NCT01208064 NCT00517790 NCT01102400 NCT00621361 NCT00460317 NCT01268059 NCT00245154 NCT00895180 NCT01005797 NCT00918203 NCT00633789 NCT01262820 NCT00693992 NCT00698815 NCT01004224 NCT00876460 NCT00326599 NCT00457392 NCT00864721 NCT00795340 NCT00922584 NCT00806819 NCT00805194 NCT00775307 NCT00411671 NCT01199822 NCT00979576 NCT00801385 NCT01019798 NCT01210053 NCT00801801 NCT00410904 NCT00735904 NCT01060514 NCT00600821 NCT00722969 NCT01027598 NCT01107652 NCT00863746 NCT01049776 NCT01069328 NCT00716534.

PMID:
22165970
PMCID:
PMC3418220
[PubMed - indexed for MEDLINE]
Free PMC Article

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