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Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
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Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
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Journal Article
Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model
2021
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ Carcinoma, Non-Small-Cell Lung - drug therapy
/ Carcinoma, Non-Small-Cell Lung - pathology
/ Carcinoma, Non-Small-Cell Lung - radiotherapy
/ Female
/ Lung Neoplasms - drug therapy
/ Lung Neoplasms - radiotherapy
/ Mice
/ Oncology
/ Phthalazines - therapeutic use
/ Piperazines - therapeutic use
/ Radiation-Sensitizing Agents - therapeutic use
/ Ribose
/ Thorax
/ Toxicity
/ Tumors
