Growth factor receptor-associated signaling pathway

Growth factor receptor-associated signaling pathways are complex networks of intracellular events triggered by the activation of cell-surface receptors, primarily receptor tyrosine kinases (RTKs), upon binding specific extracellular ligands such as EGF, VEGF, or FGF (Lemmon & Schlessinger, 2010). These pathways, including the Ras/MAPK, PI3K/Akt, and PLCγ cascades, act as central integrators of environmental signals to regulate fundamental cellular processes like growth, proliferation, survival, and metabolism (Yarden & Sliwkowski, 2001). In many human malignancies, these pathways are pathologically hijacked through receptor overexpression, gene amplification, or gain-of-function mutations, leading to autonomous signaling and uncontrolled tumor progression (Du & Lovly, 2018). Pharmacological intervention typically targets these pathways using monoclonal antibodies to block ligand binding or receptor dimerization, or small-molecule tyrosine kinase inhibitors (TKIs) that compete with ATP in the intracellular catalytic domain (Sever & Brugge, 2015). While highly effective, these therapies often face challenges such as the development of secondary resistance mutations and systemic toxicities resulting from the inhibition of these pathways in normal tissues (Sever & Brugge, 2015). Because these pathways are central to many normal physiological functions, targeting them can lead to significant side effects, such as dermatological or gastrointestinal toxicities.

Other names

RTK signaling pathwaysGrowth factor signalingReceptor tyrosine kinase signaling cascadesGrowth factor receptor signaling

Inhibition of receptor tyrosine kinase activity, blockade of ligand-receptor interaction, or modulation of downstream signaling components to arrest cell growth and induce apoptosis.