Genomic instability is a hallmark of cancer cells, which is largely caused by DNA damage repair defects. Targeting DNA damage repair pathways increases additional burdens to cancer cells and induces cancer cell lethality. This precision targeting strategy is called synthetic lethality.
DNA damage repair defects is often caused by germline or somatic mutations in DNA repair genes in cancer cells. These repair defects leads to replication stress and endangers replication fork stability. Our novel inhibitors exploit and exacerbate these vulnerabilities of cancer cells by destabilizing replication forks, which generates addition DNA damage and induces synthetic lethality in cancer cells. We believe that these agents will offer truly novel and clinically meaningful therapies for patients fighting against cancer.