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Targeting the double-strand DNA break repair pathway as a therapeutic strategy Lord CJ; Garrett MD; Ashworth AClin Cancer Res 2006[Aug]; 12 (15): 4463-8DNA repair pathways are crucial for the maintenance of genome integrity. The pathway that repairs DNA double-strand breaks (DSB) has components involved in both signaling and repairing DNA damage. Impairing DSB repair using specific inhibitors of signaling or repair might, in principle, sensitize tumor cells to particular DNA-damaging agents. Moreover, the existence of specific defects in DNA repair pathways in tumors provides the rationale for the use of "synthetic lethal" approaches targeting this cellular "Achilles' heel." Here, we discuss the mechanisms involved in DSB repair and detail potential therapeutic approaches based on targeting this pathway.|*DNA Breaks, Double-Stranded/drug effects[MESH]|*DNA Repair/drug effects[MESH]|Checkpoint Kinase 1[MESH]|Checkpoint Kinase 2[MESH]|Humans[MESH]|Models, Biological[MESH]|Protein Kinase Inhibitors/pharmacology[MESH]|Protein Kinases/drug effects/genetics/metabolism[MESH]|Protein Serine-Threonine Kinases/antagonists & inhibitors/genetics/metabolism[MESH]|Signal Transduction/drug effects[MESH]|Structure-Activity Relationship[MESH]|Tumor Suppressor Proteins/genetics[MESH] |
