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EnglishIn 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.
| Titolo: | Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors | |
| Autore/i: | Falchi, Federico; Giacomini, Elisa; Masini, Tiziana; Boutard, Nicolas; Di Ianni, Lorenza; Manerba, Marcella; Farabegoli, Fulvia; Rossini, Lara; Robertson, Janet; Minucci, Saverio; Pallavicini, Isabella; Di Stefano, Giuseppina; Roberti, Marinella; Pellicciari, Roberto; Cavalli, Andrea | |
| Autore/i Unibo: | ||
| Anno: | 2017 | |
| Rivista: | ||
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1021/acschembio.7b00707 | |
| Abstract: | 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. | |
| Data stato definitivo: | 2018-02-06T18:13:54Z | |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
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