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

doi:10.1021/acschembio.7b00707

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 journal › Article › peer-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 language	English
Pages (from-to)	2491-2497
Number of pages	7
Journal	ACS Chemical Biology
Volume	12
Issue number	10
DOIs	https://doi.org/10.1021/acschembio.7b00707
Publication status	Published - Oct 20 2017

ASJC Scopus subject areas

Biochemistry
Molecular Medicine

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Falchi, F., Giacomini, E., Masini, T., Boutard, N., Di Ianni, L., Manerba, M., Farabegoli, F., Rossini, L., Robertson, J., Minucci, S., Pallavicini, I., Di Stefano, G., Roberti, M., Pellicciari, R., & Cavalli, A. (2017). Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors. ACS Chemical Biology, 12(10), 2491-2497. https://doi.org/10.1021/acschembio.7b00707

Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors. / 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.

In: ACS Chemical Biology, Vol. 12, No. 10, 20.10.2017, p. 2491-2497.

Research output: Contribution to journal › Article › peer-review

Falchi, F, Giacomini, E, Masini, T, Boutard, N, Di Ianni, L, Manerba, M, Farabegoli, F, Rossini, L, Robertson, J, Minucci, S , Pallavicini, I , Di Stefano, G, Roberti, M, Pellicciari, R & Cavalli, A 2017, 'Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors', ACS Chemical Biology, vol. 12, no. 10, pp. 2491-2497. https://doi.org/10.1021/acschembio.7b00707

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. / Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors. In: ACS Chemical Biology. 2017 ; Vol. 12, No. 10. pp. 2491-2497.

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