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Glucocorticoids modulate tumor radiation response through a decrease in tumor oxygen consumption.

Nathalie Crokart¹, Bénédicte F Jordan, Christine Baudelet

¹Laboratories of Medicinal Chemistry and Radiopharmacy, Université Catholique de Louvain, B-1200 Brussels, Belgium.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research

|January 27, 2007

Summary

Glucocorticoids rapidly increase tumor oxygenation by reducing oxygen consumption, not supply. This enhancement improves tumor radiosensitivity, suggesting their use before irradiation therapy.

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Area of Science:

Oncology
Pharmacology
Radiotherapy

Background:

Glucocorticoids are widely used in cancer treatment for their anti-inflammatory and immunosuppressive effects.
Their potential to enhance tumor radiosensitivity by modulating tumor oxygenation remains an area of investigation.

Purpose of the Study:

To investigate the hypothesis that glucocorticoids enhance tumor radiosensitivity by increasing tumor oxygenation (pO(2)) via inhibition of mitochondrial respiration.
To evaluate the effects of hydrocortisone, dexamethasone, and prednisolone on tumor pO(2), perfusion, and oxygen consumption.

Main Methods:

Murine TLT liver tumors and FSaII fibrosarcomas were used to study the effects of glucocorticoids on pO(2).
Local pO(2) was measured using electron paramagnetic resonance (EPR).
Tumor perfusion and oxygen consumption were assessed using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and high-frequency EPR, respectively.

Main Results:

All tested glucocorticoids significantly increased tumor pO(2) within 30 minutes.
This increase in pO(2) was associated with decreased tumor perfusion and reduced global oxygen consumption.
Irradiation (25 Gy) at the time of maximum pO(2) resulted in a 1.7-fold increase in tumor radiosensitivity (regrowth delay).

Conclusions:

Glucocorticoids can enhance tumor radiosensitivity by increasing tumor oxygenation through the inhibition of mitochondrial respiration.
The findings support the potential clinical utility of administering glucocorticoids prior to radiotherapy to improve treatment outcomes.