Many cancers are deficient for certain molecular pathways and this makes them sensitive to specific drugs – a mechanism known as synthetic lethality. If molecular vulnerabilities of each tumor are identified and understood, they can be exploited to eradicate these cells. DNA damage levels and DNA repair capacity represent such potential vulnerabilities. We have discovered that some aggressive and currently treatment-resistant ovarian cancers contain high levels of innate DNA damage, while others show chemotherapy-induced persistent DNA damage signaling. This project will establish the molecular mechanisms responsible for the high DNA damage levels and how they impact tumor composition. We will also identify medications that selectively kill tumor cells with high DNA damage. The project will provide new knowledge about fundamental cellular processes at play in one of the worst-prognosis tumor types, and pave the way to novel, targeted cancer treatments.

2026

2029