[The Oxygen effect: an old new target?].

Area of Science:

• Cellular and Molecular Radiobiology
• Tumor Microenvironment Research
• Radiation Oncology

Context:

• Tumor hypoxia is a significant challenge in radiation therapy, limiting treatment efficacy.
• The oxygen effect influences cellular responses to ionizing radiation.
• Despite decades of research, effectively overcoming tumor hypoxia remains a critical goal.

Purpose:

• To review strategies for overcoming tumor hypoxia in radiation therapy.
• To discuss the role of radiosensitizing and bioreductive agents.
• To explore novel therapeutic approaches targeting hypoxia-inducible factor 1 (HIF-1) and endothelial cell pathways.

Summary:

• The oxygen effect is crucial for radiation response, with hypoxia hindering treatment. Current strategies include radiosensitizers (e.g., nimorazole) and bioreductive drugs (e.g., tirapazamine), though the latter are not standard. Emerging therapies focus on HIF-1 and endothelial pathways.
• While increasing tissue oxygenation has limited success, specific agents like nimorazole and gadolinium offer clinical benefits. Bioreductive agents like tirapazamine and AQ4N are under investigation but not routinely used.
• Research into endogenous hypoxia markers could provide predictive tools for patient response to radiation therapy and novel therapeutic interventions.

Impact:

• Identifies limitations of current hypoxia-targeting strategies in radiation oncology.
• Highlights promising new therapeutic avenues, including novel agents and pathway modulation.
• Suggests the potential utility of endogenous hypoxia markers for personalized treatment prediction.