Proto-oncogene tyrosine-protein kinase Fes (Fes (also called Fps, c-Fes, c-Fps))

Proto-oncogene tyrosine-protein kinase Fes is a human non-receptor tyrosine kinase encoded by the FES gene. It was first identified as a viral oncogene in feline and avian tumors, then cloned as a cellular proto-oncogene (c-Fes/c-Fps). Fes is mainly expressed in myeloid, endothelial, and some epithelial and neuronal cells. It acts downstream of multiple cell surface receptors, regulating the actin cytoskeleton, cell adhesion, migration, and signal transduction. Fes is involved in hematopoietic cell differentiation, mast cell function, neurite outgrowth, and immune signaling. Fes has notable roles in cancer, particularly leukemia and tumor development. It is implicated in promoting tumor angiogenesis and metastasis by influencing the tumor microenvironment and the function of tumor-associated macrophages. Genetic alterations in FES are rare but have been found in some cancers, where its function as either oncogene or tumor suppressor is context-dependent. Fes also operates downstream of KIT mutations, which drive neoplastic growth in certain hematologic tumors. While specific drugs targeting Fes are not currently marketed, it is of strong therapeutic interest, especially as a target in cancers with aberrant KIT or STAT signaling[1][2][3][4][5][6][7][8][9].

Other names

Tyrosine-protein kinase FesProto-oncogene c-FesProto-oncogene c-FpsFES (gene/protein)FPSFeline sarcoma/Fujinami avian sarcoma oncogene homologp93c-fes[1][7]

Inhibition of Fes kinase activity is being studied to block cell proliferation, angiogenesis, and metastasis in cancer settings[2][5]. Targeting Fes downstream of activated KIT receptor in diseases where KIT is constitutively active (e.g., KIT D816V mutation)[5].