Targeting the double-strand DNA break repair pathway as a therapeutic strategy.
DNA 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.
Lord
Christopher J
CJ
The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom.
Garrett
Michelle D
MD
Ashworth
Alan
A
D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D025521:Tumor Suppressor Proteins / Q000235:genetics
D047428:Protein Kinase Inhibitors; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases