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.

Key Publications

• NEWJun MET-mediated phosphorylation of YANK2 at Y282 inhibits NEDD4L-dependent SUMOylation and degradation, promoting chemoresistance in glioblastoma. (Molecular biomedicine, 2026, PMID 42337173): "This study reports a previously unrecognized MET-YANK2 signaling axis that drives glioma progression."
• NEWJun B7 homolog 3-targeted CAR-T cells secreting EGFR T-cell engagers for improved control of glioblastoma progression. (Molecular biomedicine, 2026, PMID 42301527): "Here, we investigated the expression of B7 homolog 3 (B7-H3), epidermal growth factor receptor (EGFR), and interleukin-13 receptor alpha 2 (IL-13RA2) in GBM tissues and cell lines."
• NEWJun Bisphenol A exacerbates diabetic foot ulcers through disruption of immune microenvironment and repair processes: a multi-omics analysis of environmental exposure mechanisms. (Drug and chemical toxicology, 2026, PMID 42298305): "Three core targets were identified through network analysis: BCL2, EGFR, and MMP9."
• NEWJun Self-Assembling Amphiphilic PROTACs: A Chemical Strategy for Improved EGFR-Targeted Protein Degradation. (Journal of medicinal chemistry, 2026, PMID 42284447): "Compared with the free EGFR-targeting PROTAC, PRO NPs exhibited enhanced aqueous solubility and efficient EGFR degradation in HCC827 cells."
• NEWJun [Translated article] Real world outcomes of first-line pembrolizumab in metastatic non-small-cell lung cancer. (Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria, 2026, PMID 42285782): "To describe the effectiveness and safety of pembrolizumab in routine clinical practice as first-line treatment for advanced/metastatic non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50% and without EGFR or ALK alterations."
• NEWJun Affinity Enhancement in Discrete Multivalent MegaMolecules. (Chembiochem : a European journal of chemical biology, 2026, PMID 42252776): "...nanobodies targeting epidermal growth factor receptor (EGFR) or human EGFR 2 (HER2)."
• Jun Amivantamab Monotherapy in Chemorefractory RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study. (Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2026, PMID 42013403): "Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, is approved in non-small cell lung cancer (NSCLC)."
• Mar Modeling acquired TKI resistance and effective combination therapeutic strategies in murine RET+ lung adenocarcinoma. (Cancer letters, 2026, PMID 41921856): "Cell lines derived from the selpercatinib-resistant TR.1 and TR.2 tumors exhibited in vitro sensitivity to MET and ERBB-targeted TKIs, indicating acquired bypass signaling through these receptor tyrosine kinases (RTKs)."
• Jun Biophysical Characterization of Recurrent ErbB2 Missense Mutations Reveals Alterations in Receptor Organization and Membrane Dynamics. (Journal of molecular biology, 2026, PMID 41905552): "Using confocal microscopy, Förster resonance energy transfer (FRET) and fluorescence recovery after photobleaching (FRAP), we assessed homo- and heteroassociation, lateral diffusion and tyrosine phosphorylation of ErbB2 cancer-associated variants either alone or co-expressed with EGFR."
• Jun Synthesis and evaluation of Urolithins derivatives as anticancer agents for hepatocellular carcinoma: In vitro, molecular docking, and dynamics simulations. (Bioorganic chemistry, 2026, PMID 41855633): "Moreover, integrated network pharmacology and molecular docking analyses identified several key targets, including EGFR, AKT1, MAPK1, and CASP3, suggesting a multi-target mechanism involving regulation of the PI3K/Akt and MAPK signaling pathways."