Radiation-induced prodrug activation: extending combined modality therapy for some solid tumours

Combined chemoradiotherapy is the standard of care for locally advanced solid tumours. However, systemic toxicity may limit the delivery of planned chemotherapy. New approaches such as radiation-induced prodrug activation might diminish systemic toxicity, while retaining anticancer benefit. Organic azides have recently been shown to be reduced and activated under hypoxic conditions with clinically relevant doses of radiotherapy, uncaging pazopanib and doxorubicin in preclinical models with similar efficacy as the drug, but lower systemic toxicity. This approach may be relevant to the chemoradiation of glioblastoma and other solid tumours and offers potential for switching on drug delivery from implanted devices. The inclusion of reporters to confirm drug activation, avoidance of off-target effects and synchronisation of irradiation with optimal intratumoral drug concentration will be critical. Further preclinical validation studies of this approach should be encouraged.

Automated summary

Combined chemoradiotherapy is the standard treatment for solid tumours, but systemic toxicity can limit chemotherapy delivery. Recent studies have shown that organic azides can be activated under radiation conditions, releasing drugs with reduced systemic toxicity. This approach may be relevant to glioblastoma and other solid tumours and offers potential for drug delivery from implanted devices.