Table 1 Resistance mechanisms to anti-EGFR monoclonal antibodies
Major mechanisms | Action | References |
|---|---|---|
Overexpressions of EGFR/ligands | Overexpressions of EGFR and TGF-α | |
Dysregulation of EGFR internalization and degradation by ubiquitination | EGFR is downregulated but its affinity to other activating signals are strengthened | |
MDG1 binding | MDG1-bound intracellular EGFR avoids extracellular targeting | |
Nuclear translocation of EGFR | Transcription of multiple genes or directly phosphorylates PCNA and DNA-PK | |
Enhanced SFK-mediated signaling | Promotion of EGFR nuclear translocation | |
EGFRvIII | Constitutively activated EGFR in a ligand-independent manner | |
KRAS mutation | Constant activation of EGFR downstream signals | |
PTEN loss | PI3K/AKT signal activation | |
Increased heterodimerization of EGFR or HER2 with HER3 | PI3K/AKT pathway signal enhanced | |
Crosstalks | Crosstalk with HGF-MET | |
Crosstalk with VEGF-VEGFR1 | ||
EMT | Local invasion and distant metastasis |
