Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors

Federico Falchi, Elisa Giacomini, Tiziana Masini, Nicolas Boutard, Lorenza Di Ianni, Marcella Manerba, Fulvia Farabegoli, Lara Rossini, Janet Robertson, Saverio Minucci, Isabella Pallavicini, Giuseppina Di Stefano, Marinella Roberti, Roberto Pellicciari, Andrea Cavalli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2491-2497
Number of pages7
JournalACS Chemical Biology
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 20 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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