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Abstract
Purpose: Over the last decade evidence has accumulated indicating that cell membrane-bound growth factor receptor of the erbB family and especially the epidermal growth factor receptor EGFR (erbB1) mediates resistance of tumor cells to both chemo- and radiotherapy when mutated or overexpressed. More recently a novel link between EGFR signaling pathways and DNA repair mechanisms, especially non-homologous end joining (NHEJ) repair could be demonstrated. The following review summarizes the current knowledge on the role of EGFR and its downstream signaling pathways in the regulation of cellular radiation response and DNA repair.
Conclusion: The novel findings on radiation-induced EGFR-signaling and its involvement in regulating DNA-double strand break repair need further investigations of the detailed mechanisms involved. The results to be obtained may not only improve our knowledge on basic mechanisms of radiation sensitivity/resistance but also will promote translational approaches to test new strategies for clinically applicable molecular targeting.
| Abbreviations | ||
| DNA-PKcs | = | DNA protein kinase catalytic subunit |
| EGFR | = | Epidermal growth factor receptor |
| ERK | = | Extracellular signal regulated kinase |
| GRB2 | = | Growth factor receptor-bound protein 2 |
| JNK | = | Jun N-terminal kinase |
| MEK | = | Mitogen activated extracellular signal regulated protein kinase |
| PDGF | = | Platelet derived growth factor |
| PLCγ | = | Phospholipase Cγ |
| SAPK | = | Stress activated protein kinase |
| SOS | = | Son of sevenless |
| TGFα | = | Tumor growth factor α |
| TK | = | Tyrosine kinase |
| XRCC | = | X-ray repair cross-complementing |
| Abbreviations | ||
| DNA-PKcs | = | DNA protein kinase catalytic subunit |
| EGFR | = | Epidermal growth factor receptor |
| ERK | = | Extracellular signal regulated kinase |
| GRB2 | = | Growth factor receptor-bound protein 2 |
| JNK | = | Jun N-terminal kinase |
| MEK | = | Mitogen activated extracellular signal regulated protein kinase |
| PDGF | = | Platelet derived growth factor |
| PLCγ | = | Phospholipase Cγ |
| SAPK | = | Stress activated protein kinase |
| SOS | = | Son of sevenless |
| TGFα | = | Tumor growth factor α |
| TK | = | Tyrosine kinase |
| XRCC | = | X-ray repair cross-complementing |