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Vol 6, No 5 (2010)
Review paper
Published online: 2011-01-19
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Pathophysiological basis of combination of radiotherapy and therapy directed to EGFR inhibition

Ewa Sierko, Marek Wojtukiewicz
Onkol. Prak. Klin 2010;6(5):255-263.

open access

Vol 6, No 5 (2010)
REVIEW ARTICLES
Published online: 2011-01-19

Abstract

Radiotherapy plays an import ant role in the treatment of cancer patients. Frequently failure of the treatment (locoregional progression) is observed. Overactivity of EGFR-depentent intracellular signaling contributes to tumor progression and radioresistance. Therapeutic strategies aimed at inhibition EGFR activity are an attractive perspective in terms of increasing radiosensitivity of neoplastic cells. Numerous experimental studies allowed for identification of several mechanisms underlying local tumor control after combinainterfetion of radiotherapy and therapy directed to EGFR inhibition, including: direct kill of cancer stem cells by EGFR inhibitors, cellular radiosensitization through modified signal transduction, inhibition of radiation induced-DNA damage repair, reduced repopulation or improved reoxygenation of tumor cells during fractionated radiotherapy. Clinical effects of the combined treatment are heterogeneous and depend among others on histopathological type of cancer, type of administered EGFR inhibitor, its dosage, and treatment sequence. To date, mechanism underlying these variations are not well understood. Predictive factors of such combined treatment are scant. Additional studies aimed at better understanding of efficacy and mechanisms of activity of radiotherapy combined with EGFR inhibitors with local control as an endpoint are warranted. Potential toxicity towards normal tissues of such treatment should be also assessed.

Onkol. Prak. Klin. 2010; 6, 5: 255–263

Abstract

Radiotherapy plays an import ant role in the treatment of cancer patients. Frequently failure of the treatment (locoregional progression) is observed. Overactivity of EGFR-depentent intracellular signaling contributes to tumor progression and radioresistance. Therapeutic strategies aimed at inhibition EGFR activity are an attractive perspective in terms of increasing radiosensitivity of neoplastic cells. Numerous experimental studies allowed for identification of several mechanisms underlying local tumor control after combinainterfetion of radiotherapy and therapy directed to EGFR inhibition, including: direct kill of cancer stem cells by EGFR inhibitors, cellular radiosensitization through modified signal transduction, inhibition of radiation induced-DNA damage repair, reduced repopulation or improved reoxygenation of tumor cells during fractionated radiotherapy. Clinical effects of the combined treatment are heterogeneous and depend among others on histopathological type of cancer, type of administered EGFR inhibitor, its dosage, and treatment sequence. To date, mechanism underlying these variations are not well understood. Predictive factors of such combined treatment are scant. Additional studies aimed at better understanding of efficacy and mechanisms of activity of radiotherapy combined with EGFR inhibitors with local control as an endpoint are warranted. Potential toxicity towards normal tissues of such treatment should be also assessed.

Onkol. Prak. Klin. 2010; 6, 5: 255–263

Get Citation

Keywords

EGFR; radiation therapy; DNA repair

About this article
Title

Pathophysiological basis of combination of radiotherapy and therapy directed to EGFR inhibition

Journal

Oncology in Clinical Practice

Issue

Vol 6, No 5 (2010)

Article type

Review paper

Pages

255-263

Published online

2011-01-19

Bibliographic record

Onkol. Prak. Klin 2010;6(5):255-263.

Keywords

EGFR
radiation therapy
DNA repair

Authors

Ewa Sierko
Marek Wojtukiewicz

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