Grant: Project Grant

Human papillomaviruses (HPV) infect undifferentiated stem cells of our skin. While our immune system clears most of these infections, the persistence of HPV lead to the development of cervical and oropharyngeal cancers (OPCs). Over the last decade, the number of Canadians suffering from HPV-induced OPCs has drastically increased (27% in men and 14% in women). Although patients suffering from HPV-induced OPCs generally have a good response to chemoradiation therapy, a significant proportion still exhibit a poor prognosis. To survive chemoradiation, cells rely on a sophisticated response to detect and repair the DNA damage induced by the treatment. Over the last five years, our work has revealed how components of the virus directly impair the ability of the cells to repair injured DNA properly. This project aims at elucidating the mechanisms by which host-pathogen interactions contribute to DNA damage adaptation in HPV+ OPCs and determine how it affects their resistance to chemoradiation treatments. Based on our preliminary results, we will define how these interactions impact the functions of cellular proteins that play essential roles in response to DNA injuries and determine which pathways promote survival of HPV+ cancer cells in response to treatment with DNA damaging agents used in the clinic. Globally, our findings will define how the virus rewires the response to DNA injuries and expose unique vulnerabilities that can be exploited to kill HPV+ cancer cells. By revealing cellular mechanisms used to survive high levels of DNA damage, the knowledge acquired also has the potential to apply to many tumours that experience a similar phenotype.