DNA repair inhibition: a selective tumour targeting strategy.
Advanced cancer is a leading cause of death in the developed world. Chemotherapy and radiation are the two main treatment modalities currently available. The cytotoxicity of many of these agents is directly related to their propensity to induce DNA damage. However, the ability of cancer cells to recognize this damage and initiate DNA repair is an important mechanism for therapeutic resistance and has a negative impact upon therapeutic efficacy. Pharmacological inhibition of DNA repair, therefore, has the potential to enhance the cytotoxicity of a diverse range of anticancer agents. Moreover, the use of inhibitors of DNA repair or DNA damage signalling pathways appears to provide an exciting opportunity to target the genetic differences that exist between normal and tumour tissue.
Madhusudan
Srinivasan
S
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Hickson
Ian D
ID
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D006898:Hydroxylamines / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000037:antagonists & inhibitors*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006898:Hydroxylamines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D025521:Tumor Suppressor Proteins; C005214:methoxyamine; D019853:O(6)-Methylguanine-DNA Methyltransferase; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases