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Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model

BACKGROUND: The radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithora...

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Autores principales: Jiang, Yanyan, Martin, Jennifer, Alkadhimi, Maryam, Shigemori, Kay, Kinchesh, Paul, Gilchrist, Stuart, Kersemans, Veerle, Smart, Sean, Thompson, James M., Hill, Mark A., O’Connor, Mark J., Davies, Barry R., Ryan, Anderson J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144220/
https://www.ncbi.nlm.nih.gov/pubmed/33742147
http://dx.doi.org/10.1038/s41416-021-01296-y
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author Jiang, Yanyan
Martin, Jennifer
Alkadhimi, Maryam
Shigemori, Kay
Kinchesh, Paul
Gilchrist, Stuart
Kersemans, Veerle
Smart, Sean
Thompson, James M.
Hill, Mark A.
O’Connor, Mark J.
Davies, Barry R.
Ryan, Anderson J.
author_facet Jiang, Yanyan
Martin, Jennifer
Alkadhimi, Maryam
Shigemori, Kay
Kinchesh, Paul
Gilchrist, Stuart
Kersemans, Veerle
Smart, Sean
Thompson, James M.
Hill, Mark A.
O’Connor, Mark J.
Davies, Barry R.
Ryan, Anderson J.
author_sort Jiang, Yanyan
collection PubMed
description BACKGROUND: The radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithoracic radiation in a urethane-induced mouse lung cancer model. METHODS: To assess tolerability, A/J mice were treated with olaparib plus whole thorax radiation (13 Gy), body weight changes were monitored and normal tissue effects were assessed by histology. In anti-tumour (intervention) studies, A/J mice were injected with urethane to induce lung tumours, and were then treated with olaparib alone, left thorax radiation alone or the combination of olaparib plus left thorax radiation at 8 weeks (early intervention) or 18 weeks (late intervention) after urethane injection. Anti-tumour efficacy and normal tissue effects were assessed by visual inspection, magnetic resonance imaging and histology. RESULTS: Enhanced body weight loss and oesophageal toxicity were observed when olaparib was combined with whole thorax but not hemithorax radiation. In both the early and late intervention studies, olaparib increased the anti-tumour effects of hemithoracic irradiation without increasing lung toxicity. CONCLUSIONS: The addition of olaparib increased the therapeutic index of hemithoracic radiation in a mouse model of lung cancer.
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spelling pubmed-81442202021-06-07 Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model Jiang, Yanyan Martin, Jennifer Alkadhimi, Maryam Shigemori, Kay Kinchesh, Paul Gilchrist, Stuart Kersemans, Veerle Smart, Sean Thompson, James M. Hill, Mark A. O’Connor, Mark J. Davies, Barry R. Ryan, Anderson J. Br J Cancer Article BACKGROUND: The radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithoracic radiation in a urethane-induced mouse lung cancer model. METHODS: To assess tolerability, A/J mice were treated with olaparib plus whole thorax radiation (13 Gy), body weight changes were monitored and normal tissue effects were assessed by histology. In anti-tumour (intervention) studies, A/J mice were injected with urethane to induce lung tumours, and were then treated with olaparib alone, left thorax radiation alone or the combination of olaparib plus left thorax radiation at 8 weeks (early intervention) or 18 weeks (late intervention) after urethane injection. Anti-tumour efficacy and normal tissue effects were assessed by visual inspection, magnetic resonance imaging and histology. RESULTS: Enhanced body weight loss and oesophageal toxicity were observed when olaparib was combined with whole thorax but not hemithorax radiation. In both the early and late intervention studies, olaparib increased the anti-tumour effects of hemithoracic irradiation without increasing lung toxicity. CONCLUSIONS: The addition of olaparib increased the therapeutic index of hemithoracic radiation in a mouse model of lung cancer. Nature Publishing Group UK 2021-03-19 2021-05-25 /pmc/articles/PMC8144220/ /pubmed/33742147 http://dx.doi.org/10.1038/s41416-021-01296-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jiang, Yanyan
Martin, Jennifer
Alkadhimi, Maryam
Shigemori, Kay
Kinchesh, Paul
Gilchrist, Stuart
Kersemans, Veerle
Smart, Sean
Thompson, James M.
Hill, Mark A.
O’Connor, Mark J.
Davies, Barry R.
Ryan, Anderson J.
Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
title Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
title_full Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
title_fullStr Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
title_full_unstemmed Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
title_short Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
title_sort olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144220/
https://www.ncbi.nlm.nih.gov/pubmed/33742147
http://dx.doi.org/10.1038/s41416-021-01296-y
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