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Fibroblast Growth Factor Receptor Signaling in Skin Cancers

Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland
Academic Editor: Klaus Holzmann
Cells 2019, 8(6), 540; https://doi.org/10.3390/cells8060540
Received: 15 May 2019 / Revised: 31 May 2019 / Accepted: 3 June 2019 / Published: 4 June 2019
(This article belongs to the Special Issue Fibroblast Growth Factor Receptor (FGFR) Signaling Pathway in Tumor)
Fibroblast growth factor (FGF)/Fibroblast growth factor receptor (FGFR) signaling regulates various cellular processes during the embryonic development and in the adult organism. In the skin, fibroblasts and keratinocytes control proliferation and survival of melanocytes in a paracrine manner via several signaling molecules, including FGFs. FGF/FGFR signaling contributes to the skin surface expansion in childhood or during wound healing, and skin protection from UV light damage. Aberrant FGF/FGFR signaling has been implicated in many disorders, including cancer. In melanoma cells, the FGFR expression is low, probably because of the strong endogenous mutation-driven constitutive activation of the downstream mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) signaling pathway. FGFR1 is exceptional as it is expressed in the majority of melanomas at a high level. Melanoma cells that acquired the capacity to synthesize FGFs can influence the neighboring cells in the tumor niche, such as endothelial cells, fibroblasts, or other melanoma cells. In this way, FGF/FGFR signaling contributes to intratumoral angiogenesis, melanoma cell survival, and development of resistance to therapeutics. Therefore, inhibitors of aberrant FGF/FGFR signaling are considered as drugs in combination treatment. The ongoing LOGIC-2 phase II clinical trial aims to find out whether targeting the FGF/FGFR signaling pathway with BGJ398 may be a good therapeutic strategy in melanoma patients who develop resistance to v-Raf murine sarcoma viral oncogene homolog B (BRAF)/MEK inhibitors. View Full-Text
Keywords: FGF; fibroblast growth factor; FGFR; autocrine signaling; skin; melanoma; squamous and basal cell carcinoma; seborrheic keratosis; targeted therapy; resistance FGF; fibroblast growth factor; FGFR; autocrine signaling; skin; melanoma; squamous and basal cell carcinoma; seborrheic keratosis; targeted therapy; resistance
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Czyz, M. Fibroblast Growth Factor Receptor Signaling in Skin Cancers. Cells 2019, 8, 540.

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