EGFR-MET
EGFR-MET
Overview
EGFR-MET refers to a bispecific protein target concept involving the epidermal growth factor receptor (EGFR) and MET, two receptor tyrosine kinases that are important in cell growth, survival, migration, and oncogenic signaling. In biomedical research, EGFR-MET is most often discussed in the context of therapeutic targeting rather than as a single naturally occurring protein, because dual engagement of EGFR and MET can be used to modulate compensatory signaling pathways that contribute to tumor progression and treatment resistance.
EGFR is a well-established target in non-small-cell lung cancer (NSCLC) and other epithelial malignancies, while MET is frequently implicated in bypass signaling and resistance to EGFR-directed therapies. Dual-target strategies are therefore of interest for overcoming adaptive resistance mechanisms, especially in tumors with complex receptor-network signaling involving pathways such as PI3K/Akt, MAPK signaling, and related downstream effectors. In recent research, EGFR-MET has been studied in the context of bispecific antibodies, targeted protein degradation, and multivalent binding platforms designed to improve receptor engagement and antitumor activity.
Focus of Latest Publications
Recent publications have examined EGFR-MET primarily in the context of Targeted Cancer Therapy, especially in glioblastoma and other solid tumors. One study evaluated amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, in chemorefractory metastatic colorectal cancer, reflecting continued interest in dual EGFR/MET targeting as a therapeutic strategy. Another publication on glioblastoma investigated antigen heterogeneity and immune escape in CAR-T therapy, showing that sustained B7-H3 CAR-T exposure led to B7-H3 downregulation with concurrent EGFR upregulation. To address this, investigators engineered B7-H3 CAR-T cells to secrete an EGFR-targeting bispecific T-cell engager, enabling both direct B7-H3-dependent killing and recruitment of unmodified T cells against EGFR-expressing tumor cells.
Several studies focused on EGFR as a molecular target for small-molecule and protein-degradation approaches. A self-assembling amphiphilic PROTAC nanoparticle system was developed to improve EGFR-targeted protein degradation, with the nanoparticle formulation showing enhanced aqueous solubility, efficient EGFR degradation in HCC827 cells, and potent antitumor activity in vivo with reduced systemic toxicity. In parallel, multivalent nanobody-based megamolecules targeting EGFR were shown to markedly enhance apparent binding affinity, with valency emerging as the main driver of affinity improvement. Additional medicinal chemistry studies identified novel EGFR-directed compounds with antiproliferative and pro-apoptotic activity in drug-resistant non-small-cell lung cancer cells, including derivatives that bound the EGFR kinase domain and induced cell-cycle arrest and apoptosis.
Other publications linked EGFR to broader signaling and disease mechanisms. In a multi-omics analysis of diabetic foot ulcers, EGFR emerged as one of three core targets associated with bisphenol A exposure, alongside BCL2 and MMP9, with EGFR mainly expressed in fibroblasts and epithelial cells. In hepatocellular carcinoma, network pharmacology and docking studies of urolithin derivatives identified EGFR among key targets implicated in PI3K/Akt and MAPK signaling, while biochemical validation showed suppression of AKT and ERK phosphorylation. Across these studies, EGFR-MET-related work consistently centered on receptor targeting, resistance mechanisms, and combination or engineered therapies designed to improve antitumor efficacy and overcome tumor heterogeneity or treatment failure.