Grant: Travel Awards - Institute Community Support

Head and neck cancer (HNC) ranks seventh globally, with over 660,000 new cases, 325,000 deaths annually, and an estimated 30% rise by 2030. Nonsurgical treatments for HNC mainly include radiation therapy and platinum-based DNA damaging therapies. However, the ability of cancer cells to repair DNA damage can undermine the effectiveness of these treatments. ERCC1/XPF, an enzyme complex in mammalian cells, participates in repairing DNA damage caused by radiation and chemotherapeutic agents like Cisplatin. Notably, ERCC1 overexpression was found to be associated with worse outcome in advanced HNC patients treated with cisplatin. Furthermore, High ERCC1 expression in HNC patients treated with chemoradiation was associated with poor patient survival. These findings validated ERCC1-XPF as a therapeutic target in HNC and inspired the development of a novel potent inhibitor of ERCC1/XPF by our research team at the University of Alberta. We have recently found a medication clinically used in malaria treatment, pyronaridine (PYD) to be a potent inhibitor of ERCC1/XPF that can sensitize cancer cells towards radiation therapy and treatment with cisplatin or carboplatin. Our goal in the current project is to develop new forms of PYD that can target HNC tumors while sparing normal tissues from exposure to this medication. This will be accomplished through development of carriers at nanometer size range for PYD that can direct their cargo to HNC site. This research holds immense potential to revolutionize HNC treatment by development of HNC targeted inhibitors of ERCC1/XPF that can enhance the effectiveness of radiation and chemotherapy in HNC patients against cancer while reducing the side effects of combination treatment in normal and healthy tissues.