EGFRdriven

EGFR-driven describes cancers in which signaling through the epidermal growth factor receptor (EGFR) is a primary driver of tumor growth and survival. EGFR is a transmembrane receptor tyrosine kinase. Upon ligand binding, its intracellular kinase domain is activated, triggering downstream cascades such as the RAS-RAF-MEK-ERK and PI3K-AKT-mTOR pathways that promote proliferation and survival.

In non-small cell lung cancer, activating EGFR mutations such as exon 19 deletions and L858R confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Reversible TKIs like gefitinib and erlotinib, irreversible inhibitors such as afatinib, and the third-generation osimertinib are used, with resistance commonly arising through T790M or other alterations.

In glioblastoma, EGFR amplification and the EGFRvIII variant create a constitutively active receptor but targeted therapies have yielded limited benefit due to tumor heterogeneity and delivery challenges across the blood–brain barrier.

In other tumors, EGFR alterations appear in colorectal cancer and head and neck squamous cell carcinoma. Anti-EGFR antibodies such as cetuximab and panitumumab are effective primarily in biomarker contexts like KRAS wild-type disease, and resistance can still occur through multiple mechanisms.

The concept of EGFR-driven emphasizes reliance on EGFR signaling for tumor growth and guides biomarker development and therapy decisions. Ongoing research seeks to overcome resistance, improve central nervous system targeting, and develop novel inhibitors and combination strategies, including next-generation TKIs and approaches targeting EGFR variants.