Switching On Prodrugs Using Radiotherapy

J. Geng and M. Bradley describe the use of radiotherapy to activate antitumor prodrugs.

Chemotherapy is extensively used in oncology, being highly efficient for cancer treatment. However, many commercially applied chemotherapeutic drugs have less-than-ideal selectivity for cancer cells and often do not spare normal healthy tissues/organs, thus giving rise to systemic toxicity effects in patients. The use of prodrugs is known to be an effective strategy to reduce these side effects and enhance selectivity. Prodrugs are typically chemotherapy drugs that have been chemically modified, such that they release the pharmacologically active agent upon chemical modification in vivo. Thus, when the prodrugs reach the tumor area, stimulus-triggered de-caging of the ‘modification’ takes place and releases the active drug, thus achieving precise tumor treatment.
In this collaborative work, the groups of Professors Jin Geng and Mark Bradley at the University of Edinburgh (UK) imagined an antitumor drug that could be converted into an X-ray-activatable prodrug with sufficient stability and significantly reduced toxicity compared to the naked drug, such that systemic toxicity issues can be overcome.

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