Fibroblast Growth Factor Receptor Signaling in Skin Cancers.

Fibroblast Growth Factor Receptor Signaling in Skin Cancers.

Publication date: Jun 04, 2019

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.

Czyz, M. Fibroblast Growth Factor Receptor Signaling in Skin Cancers. 22912. 2019 Cells (8):6.

Concepts Keywords
Angiogenesis Growth factors
BRAF Signal transduction
Cancer Cell biology
Clinical Trial Tyrosine kinase receptors
Endogenous Branches of biology
Endothelial Cells Skin Cancers
ERK Disorders
Extracellular Intratumoral angiogenesis melanoma
FGF MAPK/ERK pathway
FGFR Melanoma
FGFR1 Autocrine signaling
Fibroblast Growth Factor Paracrine signaling
Fibroblasts Cancer melanoma
Homolog Squamous basal carcinoma
Keratinocytes Raf murine sarcoma
Kinase Seborrheic keratosis
MAPK
MEK
Melanocytes
Melanoma
Melanomas
Mitogen
Murine
Mutation
Oncogene
Organism
Paracrine
Sarcoma
Tumor
Viral
Wound Healing

Semantics

Type Source Name
pathway BSID Basal cell carcinoma
disease DOID basal cell carcinoma
disease MESH basal cell carcinoma
disease DOID seborrheic keratosis
disease MESH seborrheic keratosis
gene UNIPROT MAP2K7
gene UNIPROT BRAF
disease DOID sarcoma
disease MESH sarcoma
gene UNIPROT ZHX2
pathway BSID Angiogenesis
gene UNIPROT FGFR1
gene UNIPROT EPHB2
gene UNIPROT MAPK1
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease DOID cancer
disease MESH cancer
gene UNIPROT MAGEE1
gene UNIPROT TNFSF14
disease MESH development
disease MESH Skin Cancers

Original Article

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