Towards new personalized treatment options for patients with genomically unstable tumors

DNA replication and transmission of the genome to daughter cells is an essential part of the life cycle of all living organisms and forms the basis of biological inheritance. Genetic variation normally occurs at a low frequency during replication and transmission of DNA and promotes biological variation and evolution.Excessive DNA damage, however, can be caused by (inherited) DNA repair defects or by exposure to environmental agents, which impacts DNA integrity. Loss of genomic integrity, or "genomic instability" refers to the accumulation of genomic alterations which is causally linked with various diseases, including cancer. Normal cells are unable to survive a high degree of genomic instability in contrast to cancer cells, which tolerate high levels of genomic instability. We aimed to unravel how genomically unstable cancer cells are "rewired" or, e.g. which escape routes cancer cells use to circumvent survival or resistance mechanisms. By pre-clinically validating potential therapeutic targets that allow survival of genomically unstable cancer cells, we were able to pinpoint to potential targets that could be of interest in the treatment of patients with genomically unstable cancers