Growth factors

Growth factors are secreted polypeptides that regulate cell proliferation, differentiation, survival, migration, and tissue organization by binding to cell-surface receptor tyrosine kinases (RTKs). Ligand binding induces receptor dimerization and autophosphorylation, which in turn activates intracellular signaling cascades—most notably the RAS-MAPK and PI3K-AKT pathways—that alter gene expression and cellular behavior. Growth factors can act in an autocrine, paracrine, or endocrine manner, and their actions are tightly regulated under normal physiological conditions.

Epidermal growth factor (EGF) binds to the EGF receptor (EGFR/ErbB), a member of the ErbB family of RTKs. EGFR activation regulates mitogenesis, survival, and differentiation in epithelial and other cell types. Its dysregulation through overexpression, mutation, or autocrine ligand production drives several cancers, particularly non-small cell lung cancer, where EGFR tyrosine kinase inhibitors have become standard therapy. Other ErbB family members, such as HER2, are also important therapeutic targets in breast and gastric cancers.

Fibroblast growth factors (FGFs) comprise eighteen secreted ligands that act on four signaling FGFRs. FGF signaling is essential for embryonic development, organogenesis, and tissue repair, and it also regulates metabolic functions in adult tissues. Aberrant FGF signaling contributes to developmental defects, metabolic disorders, and cancer, where it promotes proliferation, survival, and therapy resistance. FGF receptor inhibitors and ligand traps are being developed for cancer and metabolic diseases.

Platelet-derived growth factors (PDGFs) include four ligands—PDGF-A, PDGF-B, PDGF-C, and PDGF-D—that act on two receptors, PDGFRα and PDGFRβ. PDGF signaling controls the recruitment and proliferation of fibroblasts, smooth muscle cells, and pericytes, and is critical for wound healing and tissue repair. Dysregulated PDGF signaling promotes fibrosis, atherosclerosis, and cancer. Autocrine PDGF loops drive gliomas and sarcomas, while paracrine signaling in epithelial cancers recruits tumor stroma and supports angiogenesis and metastasis.

Vascular endothelial growth factor (VEGF) is the principal regulator of angiogenesis, the formation of new blood vessels. VEGF signaling is required for physiological vasculogenesis during development and for angiogenesis in wound healing and the female reproductive cycle. However, it also drives pathological angiogenesis in tumors and retinal diseases, where it promotes endothelial cell proliferation, migration, and vascular permeability. Anti-VEGF antibodies and receptor tyrosine kinase inhibitors are widely used in oncology and ophthalmology, though resistance and off-target effects remain significant challenges.