EGFR-targeted anti-cancer drugs in radiotherapy: preclinical evaluation of mechanisms.
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EGFR-targeted anti-cancer drugs in radiotherapy: preclinical evaluation of mechanisms. / Baumann, Michael; Krause, Mechthild; Dikomey, Ekkehard; Dittmann, Klaus; Dörr, Wolfgang; Kasten-Pisula, Ulla; Rodemann, H Peter.
In: RADIOTHER ONCOL, Vol. 83, No. 3, 3, 2007, p. 238-248.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - EGFR-targeted anti-cancer drugs in radiotherapy: preclinical evaluation of mechanisms.
AU - Baumann, Michael
AU - Krause, Mechthild
AU - Dikomey, Ekkehard
AU - Dittmann, Klaus
AU - Dörr, Wolfgang
AU - Kasten-Pisula, Ulla
AU - Rodemann, H Peter
PY - 2007
Y1 - 2007
N2 - Preclinical and clinical results indicate that the EGFR can mediate radioresistance in different solid human tumours. Combination of radiotherapy and EGFR inhibitors can improve local tumour control compared to irradiation alone and has been introduced into clinical radiotherapy practice. So far several mechanisms have been identified in preclinical studies to contribute to improved local tumour control after radiation combined with EGFR inhibitors. These include direct kill of cancer stem cells by EGFR inhibitors, cellular radiosensitization through modified signal transduction, inhibition of repair of DNA damage, reduced repopulation and improved reoxygenation during fractionated radiotherapy. Effects and mechanisms may differ for different classes of EGFR inhibitors, for different tumours and for normal tissues. The mechanisms underlying this heterogeneity are currently poorly understood, and predictive assays are not available yet. Importantly, mechanisms and predictors for the combined effects of radiation with EGFR inhibitors appear to be considerably different to those for application of EGFR inhibitors alone or in combination with chemotherapy. Therefore to further evaluate the efficacy and mechanisms of EGFR-inhibition in combined treatments, radiotherapy-specific preclinical research strategies, which include in vivo experiments using local tumour control as an endpoint, as well as animal studies on normal tissue toxicity are needed.
AB - Preclinical and clinical results indicate that the EGFR can mediate radioresistance in different solid human tumours. Combination of radiotherapy and EGFR inhibitors can improve local tumour control compared to irradiation alone and has been introduced into clinical radiotherapy practice. So far several mechanisms have been identified in preclinical studies to contribute to improved local tumour control after radiation combined with EGFR inhibitors. These include direct kill of cancer stem cells by EGFR inhibitors, cellular radiosensitization through modified signal transduction, inhibition of repair of DNA damage, reduced repopulation and improved reoxygenation during fractionated radiotherapy. Effects and mechanisms may differ for different classes of EGFR inhibitors, for different tumours and for normal tissues. The mechanisms underlying this heterogeneity are currently poorly understood, and predictive assays are not available yet. Importantly, mechanisms and predictors for the combined effects of radiation with EGFR inhibitors appear to be considerably different to those for application of EGFR inhibitors alone or in combination with chemotherapy. Therefore to further evaluate the efficacy and mechanisms of EGFR-inhibition in combined treatments, radiotherapy-specific preclinical research strategies, which include in vivo experiments using local tumour control as an endpoint, as well as animal studies on normal tissue toxicity are needed.
M3 - SCORING: Zeitschriftenaufsatz
VL - 83
SP - 238
EP - 248
JO - RADIOTHER ONCOL
JF - RADIOTHER ONCOL
SN - 0167-8140
IS - 3
M1 - 3
ER -
