DNA repair inhibitors and synthetic lethal strategies

In most developping countries, cancer is the main cause of human death with cardiovascular diseases. The initial event for cancer formation is mutations in the genetic material. In recent years, it has been increasing clear that mutations in DNA repair enzymes contribute to genome instability and cancer. Increasing DNA damage in cancerous cells through radiotherapy or chemotherapy has been useful treatments for cancer. However, these approaches have several drawbacks including secondary mutations in healthy cells. Hence, we need to design more clever, and efficient approaches to kill cancer cells in the context of personalized medicine. Synthetic lethality is an approach to study selective cell killing where inactivation of two pathways leads to cell death  whereas a mutation in only one of these pathways does not, and by itself is said to be viable.  We are currently working to develop a synthetic lethal strategy  that will kill only the cells mutated in the tumor suppressors BRCA1, BRCA2, or PALB2 and spare normal cells.