EGFRMAPK

EGFRMAPK refers to the signaling axis that connects the epidermal growth factor receptor (EGFR) to the mitogen-activated protein kinase (MAPK) cascade. The pathway is typically activated when ligands such as epidermal growth factor bind EGFR, causing receptor dimerization and autophosphorylation. Phosphotyrosines on the receptor recruit adaptor proteins like GRB2 and SHC, which in turn bring in SOS to activate the small GTPase Ras. Active Ras then activates the Raf kinase, which phosphorylates MEK, and MEK phosphorylates ERK1/2. Activated ERK translocates to the nucleus to regulate transcription factors and control gene expression programs that influence cell proliferation, differentiation, survival, and migration. The EGFR-MAPK signaling module is tightly regulated by phosphatases, scaffold proteins, and feedback mechanisms, and it interacts with other pathways such as PI3K/AKT.

Physiological roles of EGFRMAPK include development, tissue homeostasis, and wound healing, where precise modulation of cell growth and differentiation is essential. In pathological states, especially cancer, aberrant EGFR-MAPK signaling can promote uncontrolled cell proliferation and survival. Aberrations can arise from EGFR amplification or mutation, overexpression of ligands, or activating mutations in downstream components such as Ras or BRAF, leading to constitutive pathway activity.

Therapeutic relevance centers on targeting this axis. EGFR inhibitors (for example, cetuximab, gefitinib, erlotinib) and downstream MAPK inhibitors (such as MEK inhibitors) are used in various cancers, often with combination approaches to overcome resistance. Resistance mechanisms include downstream mutations, alternative receptor signaling, or feedback activation of parallel pathways, underscoring the need for biomarker-guided and multi-target strategies.