The article "DNA Repair Pathways as Targets for Cancer Therapy" by Helleday et al. discusses the potential of targeting DNA repair pathways in cancer therapy. Chemotherapy often causes DNA damage that leads to replication-dependent toxic lesions, and cells have overlapping DNA damage repair pathways to survive these treatments. Inhibitors of DNA repair can be used in combination with DNA-damaging drugs to enhance their efficacy. Since DNA repair pathways are frequently altered in tumors, cancer cells often rely on a subset of these pathways for survival, making them potential targets for inhibition. DNA repair inhibitors can act as single agents to selectively kill cancer cells, as they increase unrepaired endogenous DNA damage in tumor cells, potentially reducing side effects in non-cancerous cells. The article also explores the use of DNA repair inhibitors to amplify oncogene- or hypoxia-induced replication stress and convert these lesions into fatal replication lesions. Additionally, it highlights the importance of exploiting tumor-specific replication stress and endogenous DNA damage for targeted cancer treatment. The authors conclude that while DNA repair inhibitors have shown promise in enhancing current therapies, their most attractive use may be in exploiting cancer defects to achieve more selective cell killing, particularly in DNA repair-defective tumors.The article "DNA Repair Pathways as Targets for Cancer Therapy" by Helleday et al. discusses the potential of targeting DNA repair pathways in cancer therapy. Chemotherapy often causes DNA damage that leads to replication-dependent toxic lesions, and cells have overlapping DNA damage repair pathways to survive these treatments. Inhibitors of DNA repair can be used in combination with DNA-damaging drugs to enhance their efficacy. Since DNA repair pathways are frequently altered in tumors, cancer cells often rely on a subset of these pathways for survival, making them potential targets for inhibition. DNA repair inhibitors can act as single agents to selectively kill cancer cells, as they increase unrepaired endogenous DNA damage in tumor cells, potentially reducing side effects in non-cancerous cells. The article also explores the use of DNA repair inhibitors to amplify oncogene- or hypoxia-induced replication stress and convert these lesions into fatal replication lesions. Additionally, it highlights the importance of exploiting tumor-specific replication stress and endogenous DNA damage for targeted cancer treatment. The authors conclude that while DNA repair inhibitors have shown promise in enhancing current therapies, their most attractive use may be in exploiting cancer defects to achieve more selective cell killing, particularly in DNA repair-defective tumors.