Targeting the replication stress response through synthetic lethal strategies in cancer medicine

Elevated replicative stress in cancer cells stemming from endogenous and exogenous genotoxic stressors is a targetable vulnerability for exploitation. Inhibiting key kinases of the replicate stress response (RSR) cascade, including ATM, ATR, CHK1/2, WEE1, DNA-dependent protein kinase (DNA-PK), amongst others, abrogates cell cycle checkpoints, allowing aberrant cell cycle progression and culminating in mitotic catastrophe. Several drug candidates...