Targeting the fibroblast growth factor receptor family in cancer

Hallinan, Niamh, Finn, Stephen, Cuffe, Sinead, Rafee, Shereen, O’Byrne, Kenneth, & Gately, Kathy (2016) Targeting the fibroblast growth factor receptor family in cancer. Cancer Treatment Reviews, 46, pp. 51-62.

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Fibroblast growth factors (FGFs) regulate a plethora of biological functions, in both the embryonic and adult stages of development, binding their cognate receptors and thus activating a variety of downstream signalling pathways. Deregulation of the FGF/FGFR signalling axis, observed in multifarious tumor types including squamous non-small cell lung cancer, occurs through genomic FGFR alterations that drive ligand-independent receptor signalling or alterations that support ligand-dependent activation. Mutations are not restricted to the tyrosine kinase domain and aberrations appear to be tumor type dependent. As well as its complementarity and synergy with VEGF of particular interest is the interplay between FGFR and EGFR and the ability of these pathways to offer a compensatory signalling escape mechanism when either is inhibited. Hence there exists a rationale for a combinatorial approach to inhibition of these dysregulated pathways to reverse drug resistance. To date, several multi-target tyrosine kinase inhibitors as well as FGFR specific tyrosine kinase inhibitors (TKIs), monoclonal antibodies and FGF ligand traps have been developed. Promising preclinical data has resulted in several drugs entering clinical trials. This review explores aberrant FGFR and its potential as a therapeutic target in solid tumors.

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ID Code: 95341
Item Type: Journal Article
Refereed: Yes
Keywords: FGFR; FGF ligand; EGFR; Receptor tyrosine kinase; Targeted therapy
DOI: 10.1016/j.ctrv.2016.03.015
ISSN: 0305-7372
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2016 Elsevier Ltd.
Copyright Statement: This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Deposited On: 02 May 2016 23:54
Last Modified: 08 May 2016 04:48

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