OLAPARIB :A 10 year development journey
Early Clinical Trials:
HGSOC an ideal environment for PARP Inhibitors
´
success
PARP
DNA damage
(SSBs)
DNA replication
(accumulation of DNA DSBs)
Normal cell
with functional HR
pathway
HR-deficient tumor cell(
HRD)
(
e.g. mut BRCA 1/2 )
Cell survival
Cell death
HR-mediated
DNA repair
Tumor-selective cytotoxicity
PARP inhibitor Agents
Farmer H
et al. Nature
2005;434:917–921
Bryant HE
et al. Nature
2005;434:913–917
McCabe N
et al. Cancer Res
2006;66:8109–8115
mutBRCA: 20%
