Fibroblast Growth Factor

Thalidomide and celecoxib effectively suppress the action of FGF.

The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs). Activated FGFRs mediate interaction with the RAS-MAPK, PI3K-AKT, PLCƒÁ, and STAT intracellular signaling pathways. Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning. Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer.

Further results suggested that thalidomide inhibition of DNA synthesis, induction of apoptosis, and down-regulation of VEGF and IL-6 might be dependent on FGFR3-associated signal transduction of the ERK and STAT3 phosphorylation pathway. Thus, FGFR3 may be a predictive/surrogate marker for selection of thalidomide treatment in myeloma.