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Growth Factor Signaling and Radiotherapy to Encompass Both EGFR and TGFβ

Radiation-induced EGFR-signaling and control of DNA-damage repair

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Pages 781-791 | Received 07 Aug 2007, Accepted 25 Oct 2007, Published online: 03 Jul 2009
 

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

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