Grant: Project Grant

Radiation and chemotherapy remain the principal treatments for inoperable cancers. Cancer cells are killed following these therapies, but some are resistant due to their ability to repair the DNA damage. Recently, drugs that can block a cancer cell's ability to repair its DNA have entered in clinical trials. However, the success of these new drugs will be limited by their effects in the healthy tissues that also receive damage during treatment. To address this critical problem, we are participating in the development of a tumour-targeted DNA repair inhibitor which will preferentially sensitize cancer cells over normal tissues to treatment. To achieve this, these targeted drugs use the unique, hypoxic zones within tumours, regions of decreased oxygenation, as an engine release an activate compound that then sensitizes the resistant cancer cells to treatment. To date, we have succeeded in developing and testing over 1,000 DNA repair inhibitors, many with excellent activity. We now need to optimize the targeted prodrugs and select clinical candidates to progress to human trials.