Epidermal growth factor receptor (EGFR), Fibroblast growth factor receptor (FGFR), and Abelson tyrosine kinase (ABL1) (EGFR, FGFR, Abl)

The target entry EGFR, FGFR, Abl refers to a combination of three distinct tyrosine kinases: the Epidermal Growth Factor Receptor (EGFR), the Fibroblast Growth Factor Receptor (FGFR) family, and the Abelson tyrosine kinase (ABL1). EGFR and FGFR are transmembrane receptors that trigger intracellular signaling cascades in response to extracellular growth factors, playing vital roles in cell proliferation, differentiation, and angiogenesis (UniProt P00533, P11362). Abl is a non-receptor tyrosine kinase involved in regulating the cell cycle and DNA damage response, and its dysregulation—most notably through the BCR-ABL fusion—is a primary driver of chronic myeloid leukemia (PubMed: 29070620). These proteins are significant therapeutic targets in oncology, with various small-molecule inhibitors designed to block their catalytic activity by competing for the ATP-binding site. For instance, EGFR inhibitors like erlotinib are used in lung cancer, while FGFR inhibitors like pemigatinib are used in cholangiocarcinoma, and Abl inhibitors like imatinib are standard for leukemia. Some multi-kinase inhibitors, such as ponatinib, exhibit activity against both Abl and FGFR, illustrating the overlap in kinase domain structures. Because this entry groups three separate gene products with distinct biological functions and disease associations, it is considered a multi-target profile rather than a single canonical target.

Other names

ErbB-1HER1CD331CD332CD333CD334c-AblABL1p150BCR-ABLProto-oncogene c-Abl

Small-molecule inhibitors act as ATP-competitive antagonists that bind to the catalytic kinase domain of these proteins. This binding prevents autophosphorylation and the subsequent activation of downstream signaling cascades, such as the MAPK/ERK, PI3K/AKT, and STAT pathways, which are essential for tumor cell growth, survival, and resistance to apoptosis (PubMed: 28456782, StatPearls: NBK542231).