The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines

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The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines. / Güster, Julian David; Weissleder, Stephanie Valerie; Busch, Chia-Jung; Kriegs, Malte; Petersen, Cordula; Knecht, Rainald; Dikomey, Ekkehard; Rieckmann, Thorsten.

in: RADIOTHER ONCOL, Jahrgang 113, Nr. 3, 01.12.2014, S. 345-51.

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@article{34ca1867bd7d4c61999474989dd324f0,
title = "The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines",
abstract = "BACKGROUND AND PURPOSE: HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells.MATERIALS AND METHODS: Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay.RESULTS: Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1.CONCLUSIONS: PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity.",
author = "G{\"u}ster, {Julian David} and Weissleder, {Stephanie Valerie} and Chia-Jung Busch and Malte Kriegs and Cordula Petersen and Rainald Knecht and Ekkehard Dikomey and Thorsten Rieckmann",
note = "Copyright {\textcopyright} 2014 Elsevier Ireland Ltd. All rights reserved.",
year = "2014",
month = dec,
day = "1",
doi = "10.1016/j.radonc.2014.10.011",
language = "English",
volume = "113",
pages = "345--51",
journal = "RADIOTHER ONCOL",
issn = "0167-8140",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

RIS

TY - JOUR

T1 - The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines

AU - Güster, Julian David

AU - Weissleder, Stephanie Valerie

AU - Busch, Chia-Jung

AU - Kriegs, Malte

AU - Petersen, Cordula

AU - Knecht, Rainald

AU - Dikomey, Ekkehard

AU - Rieckmann, Thorsten

N1 - Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - BACKGROUND AND PURPOSE: HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells.MATERIALS AND METHODS: Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay.RESULTS: Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1.CONCLUSIONS: PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity.

AB - BACKGROUND AND PURPOSE: HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells.MATERIALS AND METHODS: Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay.RESULTS: Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1.CONCLUSIONS: PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity.

U2 - 10.1016/j.radonc.2014.10.011

DO - 10.1016/j.radonc.2014.10.011

M3 - SCORING: Journal article

C2 - 25467050

VL - 113

SP - 345

EP - 351

JO - RADIOTHER ONCOL

JF - RADIOTHER ONCOL

SN - 0167-8140

IS - 3

ER -