DNA damage response and reactive oxygen species-related pathways (DDR/ROS pathways)

The DNA damage response (DDR) and reactive oxygen species (ROS)-related pathways constitute a sophisticated cellular network designed to preserve genomic stability and manage oxidative stress (Jackson & Bartek, 2009, Nature). The DDR identifies and repairs DNA lesions—such as single-strand and double-strand breaks—through coordinated signaling involving sensors like ATM and ATR and effectors like PARP (Lord & Ashworth, 2017, Science). Simultaneously, ROS-related pathways regulate the levels of reactive oxygen species, which are natural byproducts of metabolism that can cause significant oxidative damage to DNA, proteins, and lipids if not neutralized by antioxidant systems (Srinivas et al., 2019, Free Radic Biol Med). In oncology, these pathways are frequently exploited; for instance, PARP inhibitors are used to induce synthetic lethality in tumors with existing DNA repair defects, such as those with BRCA mutations (O'Connor, 2015, Mol Cell). Furthermore, modulating ROS levels can sensitize cancer cells to therapy or directly trigger programmed cell death, making these pathways critical focal points for therapeutic intervention and drug development (Gorrini et al., 2013, Nat Rev Drug Discov).

Other names

DDR pathwaysROS signalingOxidative stress responseDNA repair pathwaysRedox homeostasis signaling

Inhibition of DNA repair enzymes (e.g., PARP, ATR, ATM) to induce synthetic lethality in repair-deficient cells; modulation of cellular redox state to induce oxidative stress-mediated apoptosis; potentiation of DNA-damaging chemotherapy or radiotherapy.