Targeting poly(ADP-ribosyl)ation: a promising approach in cancer therapy.
Recent progress in the field of DNA repair has demonstrated that transient inhibition of DNA damage detection or repair using potent poly(ADP-ribose) polymerase (PARP) inhibitors could improve the efficacy of cancer treatments. Although more study is needed, recent publications lead to optimism that the inhibition of poly(ADP-ribose) synthesis could selectively kill cancer cells when used to treat tumours with defective BRCA proteins. These reports and others shed some light on the DNA damage signalling and repair processes involving PARPs. However, a better understanding of the molecular mechanisms regulated by poly(ADP-ribose) metabolism will be essential before optimism can be replaced by clinical realization.
Haince
Jean-François
JF
Health and Environment Unit, Laval University Hospital Research Center, CHUQ, Faculty of Medicine, Laval University, Québec, Canada.
Rouleau
Michèle
M
Hendzel
Michael J
MJ
Masson
Jean-Yves
JY
Poirier
Guy G
GG
D004260:DNA Repair / Q000187:drug effects*; D040461:Gene Components; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy*; D010616:Phenanthrenes / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D052999:Quinazolinones; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
C487403:2-(3-(4-(4-chlorophenyl)-1-piperazinyl) propyl)-4(3H)-quinazolinone; C481203:CEP-6800; D006576:Heterocyclic Compounds, 4 or More Rings; C491685:INO 1001; D007211:Indoles; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; C115774:NU 1025; D010616:Phenanthrenes; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011799:Quinazolines; D052999:Quinazolinones; D011065:Poly(ADP-ribose) Polymerases