DNA Repair Pathways (DDR)

DNA repair pathways are a sophisticated network of cellular mechanisms, often collectively termed the DNA Damage Response (DDR), that identify and correct DNA lesions to preserve genomic integrity [1.1.2]. These pathways include Base Excision Repair (BER), Nucleotide Excision Repair (NER), Mismatch Repair (MMR), and Double-Strand Break (DSB) repair mechanisms like Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ) [1.1.2, 1.3.3]. In many cancers, specific repair pathways are compromised (e.g., BRCA1/2 mutations in HR), creating a dependency on remaining pathways for survival [1.3.4]. This vulnerability is therapeutically exploited through synthetic lethality, where inhibitors like PARP inhibitors selectively kill repair-deficient tumor cells while sparing healthy ones [1.2.2, 1.3.4]. Additionally, inhibitors of DDR signaling kinases such as ATR, ATM, and WEE1 are being investigated to enhance the efficacy of DNA-damaging chemotherapy and radiotherapy [1.2.5, 1.3.3].

Other names

DNA Damage ResponseDDRDNA Repair MechanismsGenome Maintenance Pathways

Inhibition of specific DNA repair enzymes to induce synthetic lethality in repair-deficient cells or to sensitize cells to genotoxic agents like chemotherapy and radiation.