TY - JOUR
T1 - Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors
AU - Falchi, Federico
AU - Giacomini, Elisa
AU - Masini, Tiziana
AU - Boutard, Nicolas
AU - Di Ianni, Lorenza
AU - Manerba, Marcella
AU - Farabegoli, Fulvia
AU - Rossini, Lara
AU - Robertson, Janet
AU - Minucci, Saverio
AU - Pallavicini, Isabella
AU - Di Stefano, Giuseppina
AU - Roberti, Marinella
AU - Pellicciari, Roberto
AU - Cavalli, Andrea
PY - 2017/10/20
Y1 - 2017/10/20
N2 - In BRCA2-defective cells, poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors can trigger synthetic lethality, as two independent DNA-repairing mechanisms are simultaneously impaired. Here, we have pharmacologically induced synthetic lethality, which was triggered by combining two different small organic molecules. When administered with a BRCA2-Rad51 disruptor in nonmutant cells, Olaparib showed anticancer activity comparable to that shown when administered alone in BRCA2-defective cells. This strategy could represent an innovative approach to anticancer drug discovery and could be extended to other synthetic lethality pathways.
AB - In BRCA2-defective cells, poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors can trigger synthetic lethality, as two independent DNA-repairing mechanisms are simultaneously impaired. Here, we have pharmacologically induced synthetic lethality, which was triggered by combining two different small organic molecules. When administered with a BRCA2-Rad51 disruptor in nonmutant cells, Olaparib showed anticancer activity comparable to that shown when administered alone in BRCA2-defective cells. This strategy could represent an innovative approach to anticancer drug discovery and could be extended to other synthetic lethality pathways.
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U2 - 10.1021/acschembio.7b00707
DO - 10.1021/acschembio.7b00707
M3 - Article
C2 - 28841282
AN - SCOPUS:85031909931
VL - 12
SP - 2491
EP - 2497
JO - ACS Chemical Biology
JF - ACS Chemical Biology
SN - 1554-8929
IS - 10
ER -