BRCA
+/+
BRCA
-/-
BRCA
+/-
1000x
OLAPARIB :A 10 year development journey
Preclinical:
PARP Inhibitors: Mechanism of Action
Synthetic Lethality
Farmer et al, Nature 434917-921 , 2005
Bryant et al, Nature 434922-926 ,2005
A mutation in either of two genes individually has
no effect but combining the mutations leads to
death.
In cancer cells, inhibiting one of these genes
when the other is defective should be
selectively
lethal to the tumor cells in cancer
In the case of DNA Damage Repair, this state of
dual non-funcionality can be achieved by
enzimatic inhibition of PARP in the context of
genetic mutations in BRCA-1 or BRCA-2 genes.
