TY - JOUR
T1 - Epidermal growth factor receptor and its inhibition in radiotherapy
T2 - In vivo findings
AU - Milas, L.
AU - Mason, K. A.
AU - Ang, K. K.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/7
Y1 - 2003/7
N2 - Increasing evidence shows that dysregulated epidermal growth factor receptor (EGFR) signalling plays an important part in neoplasia. When over expressed or mutated, EGFR is frequently associated with more aggressive tumour growth, poor patient prognosis and resistance of tumours to cytotoxic agents, including radiation. The present studies with murine carcinomas showed that there is an inverse correlation between the level of EGFR and tumour radiocurability. Likewise, the present clinical study in patients with head and neck cancer shows that EGFR over expression correlates with poorer tumour response to radiotherapy. Adding EGFR to tumour cells in vitro protected cells against the cytotoxic action of radiation, whereas blocking EGFR with anti-EGFR antibodies enhanced cell radiosensitivity. A casual relationship between EGFR and increased cellular resistance to radiation was established by transferring the EGFR gene into low EGFR-expressing radiosensitive tumour cells, which then become radioresistant. Radiation activated EGFR and its downstream signalling pathways in radioresistant but not in radiosensitive tumours, and this effect was associated with increased resistance to radiation, and enhanced repopulation in irradiated tumours. Increasing evidence shows that blockage of EGFR or interference with any of the steps in its signal transduction cascade can counteract negative outcomes of EGFR signalling, which has recently been explored as a therapeutic strategy in cancer treatment. The present findings demonstrate that treatment of human tumour xenografts with C225, an anti-EGFR monoclonal antibody, dramatically enhanced tumour response to radiation. Overall, the findings show that over expression of EGFR may serve as a predictor of tumour treatment outcome by radiotherapy and as a therapeutic target to enhance the efficacy of radiotherapy.
AB - Increasing evidence shows that dysregulated epidermal growth factor receptor (EGFR) signalling plays an important part in neoplasia. When over expressed or mutated, EGFR is frequently associated with more aggressive tumour growth, poor patient prognosis and resistance of tumours to cytotoxic agents, including radiation. The present studies with murine carcinomas showed that there is an inverse correlation between the level of EGFR and tumour radiocurability. Likewise, the present clinical study in patients with head and neck cancer shows that EGFR over expression correlates with poorer tumour response to radiotherapy. Adding EGFR to tumour cells in vitro protected cells against the cytotoxic action of radiation, whereas blocking EGFR with anti-EGFR antibodies enhanced cell radiosensitivity. A casual relationship between EGFR and increased cellular resistance to radiation was established by transferring the EGFR gene into low EGFR-expressing radiosensitive tumour cells, which then become radioresistant. Radiation activated EGFR and its downstream signalling pathways in radioresistant but not in radiosensitive tumours, and this effect was associated with increased resistance to radiation, and enhanced repopulation in irradiated tumours. Increasing evidence shows that blockage of EGFR or interference with any of the steps in its signal transduction cascade can counteract negative outcomes of EGFR signalling, which has recently been explored as a therapeutic strategy in cancer treatment. The present findings demonstrate that treatment of human tumour xenografts with C225, an anti-EGFR monoclonal antibody, dramatically enhanced tumour response to radiation. Overall, the findings show that over expression of EGFR may serve as a predictor of tumour treatment outcome by radiotherapy and as a therapeutic target to enhance the efficacy of radiotherapy.
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U2 - 10.1080/0955300031000114747
DO - 10.1080/0955300031000114747
M3 - Article
C2 - 14530163
AN - SCOPUS:0142216254
SN - 0955-3002
VL - 79
SP - 539
EP - 545
JO - International journal of radiation biology
JF - International journal of radiation biology
IS - 7
ER -