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Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 3/2015

Open Access 01-09-2015 | Clinical

Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications

Authors: Teresa Helsten, Maria Schwaederle, Razelle Kurzrock

Published in: Cancer and Metastasis Reviews | Issue 3/2015

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Abstract

Fibroblast growth factors (FGFs) and their receptors (FGFRs) are transmembrane growth factor receptors with wide tissue distribution. FGF/FGFR signaling is involved in neoplastic behavior and also development, differentiation, growth, and survival. FGFR germline mutations (activating) can cause skeletal disorders, primarily dwarfism (generally mutations in FGFR3), and craniofacial malformation syndromes (usually mutations in FGFR1 and FGFR2); intriguingly, some of these activating FGFR mutations are also seen in human cancers. FGF/FGFR aberrations reported in cancers are mainly thought to be gain-of-function changes, and several cancers have high frequencies of FGFR alterations, including breast, bladder, or squamous cell carcinomas (lung and head and neck). FGF ligand aberrations (predominantly gene amplifications) are also frequently seen in cancers, in contrast to hereditary syndromes. There are several pharmacologic agents that have been or are being developed for inhibition of FGFR/FGF signaling. These include both highly selective inhibitors as well as multi-kinase inhibitors. Of note, only four agents (ponatinib, pazopanib, regorafenib, and recently lenvatinib) are FDA-approved for use in cancer, although the approval was not based on their activity against FGFR. Perturbations in the FGFR/FGF signaling are present in both inherited and malignant diseases. The development of potent inhibitors targeting FGF/FGFR may provide new tools against disorders caused by FGF/FGFR alterations.
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Metadata
Title
Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications
Authors
Teresa Helsten
Maria Schwaederle
Razelle Kurzrock
Publication date
01-09-2015
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 3/2015
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-015-9579-8

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