Lay summary
Drugs used to treat cancer need to be targeted to tumours, otherwise the therapy might fail and the patient will experience side effects. Carrying drugs in an inactive form (prodrug) and then releasing the active drug at the tumour site can reduce side-effects, but limitations still exist. We will investigate a new way to activate prodrugs specifically at the tumour using a bioorthogonal chemical reaction. A small chemical reagent will be attached to a tumour-specific targeting ligand that seeks out tumour cells and sticks to them. The pre-targeted reagent will then “catch" the prodrug and “release” the active drug. New Zealand has one of the highest rates of colorectal cancer in the world and there is a high disparity for Māori patients who are 46% more likely to die than non-Māori patients. Therefore, we will exemplify our strategy in a colorectal cancer model, building New Zealand’s capacity in cancer-targeted prodrugs.