The DNA Damage Response (DDR) Network

DNA Damage Response (DDR) network is a system of cellular pathways that monitor, signal and repair DNA damage. In cancer cells, replication stress induced by oncogenes (e.g., MYC or RAS) or genetic mutations in DNA repair machinery (e.g., BRCA1 or FA) combined with loss of function in tumor suppressors (e.g., TP53 or ATM) results in persistent DNA damage and genomic instability. Targeted inhibition of the remaining components of the DDR network, such as by SRA737 or SRA141, may be synthetically lethal to cancer cells and have utility as a monotherapy in a range of tumor indications.