Targeting DNA repair as a promising approach in cancer therapy.
An increased DNA-repair activity in tumour cells has been associated with resistance to treatment to DNA-directed drugs, while defects in DNA repair pathways result in hypersensitivity to these agents. In the past years the unravelling of the molecular basis of these DNA pathways, with a better understanding of the DNA damage caused by different anticancer agents, has provided the rationale for the use of some DNA repair inhibitors to optimise the therapeutic use of DNA-damaging agents currently used in the treatment of tumours. In addition, the possibility to specifically target the differences in DNA repair capacity between normal and tumour cells has recently emerged as an exciting possibility. The present review will mainly cover those approaches that are currently under clinical investigation.
Damia
Giovanna
G
Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy.
D'Incalci
Maurizio
M
D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019853:O(6)-Methylguanine-DNA Methyltransferase