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Article

Preclinical Studies on the Effect of Rucaparib in Ovarian Cancer: Impact of BRCA2 Status

1
Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK
2
Mount Vernon Cancer Centre, Rickmansworth Road, Northwood HA6 2RN, UK
3
Division of Thoracic Surgery, The Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, Harefield, Uxbridge UB9 6JH, UK
*
Authors to whom correspondence should be addressed.
Academic Editors: Evangelos Kolettas and Vassilis Gorgoulis
Cells 2021, 10(9), 2434; https://doi.org/10.3390/cells10092434
Received: 28 July 2021 / Revised: 9 September 2021 / Accepted: 10 September 2021 / Published: 15 September 2021
(This article belongs to the Special Issue The DNA Damage Response in Cell Physiology and Disease)
Background: Approximately 50% of ovarian cancer patients harbour homologous recombination repair deficiencies. These deficiencies have been successfully targeted using poly (ADP-ribose) polymerase inhibitors (PARPi) particularly for patients harbouring BRCA1/2 mutations. The aim of this study is to assess the effects of the PARPi rucaparib in vitro using cell lines with BRCA2 mutations in comparison to those with BRCA2 wild type. Methods: Cell proliferation assays, RT-qPCR, immunofluorescence, annexin V/PI assays were used to assess the effects of rucaparib in vitro. Results: The BRCA2 mutant ovarian cancer cell line PEO1 exhibited higher PARP1 activity when treated with H2O2 compared to wild type cell lines. The migratory and proliferative capacity of PEO1 cells was compromised following treatment with rucaparib 10 µM compared to BRCA2 wild-type cell lines via a mechanism involving the mTOR pathway. Rucaparib treatment significantly increased DNA damage primarily in PEO1 cells and SKOV3 cells compared with wild type. Conclusions: Appropriate identification of robust predictive biomarkers for homologous recombination deficiency using ‘liquid’ biopsies would facilitate the identification of patients suitable for PARPi therapy. Preliminary efforts to undertake such testing are described here. This study also demonstrates the mechanisms of action of rucaparib (PARPi) which may involve elements of the mTOR pathway. View Full-Text
Keywords: ovarian cancer; PARP inhibitors; rucaparib; BRCA mutation; homologous recombination deficiency ovarian cancer; PARP inhibitors; rucaparib; BRCA mutation; homologous recombination deficiency
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MDPI and ACS Style

Saravi, S.; Alizzi, Z.; Tosi, S.; Hall, M.; Karteris, E. Preclinical Studies on the Effect of Rucaparib in Ovarian Cancer: Impact of BRCA2 Status. Cells 2021, 10, 2434. https://doi.org/10.3390/cells10092434

AMA Style

Saravi S, Alizzi Z, Tosi S, Hall M, Karteris E. Preclinical Studies on the Effect of Rucaparib in Ovarian Cancer: Impact of BRCA2 Status. Cells. 2021; 10(9):2434. https://doi.org/10.3390/cells10092434

Chicago/Turabian Style

Saravi, Sayeh, Zena Alizzi, Sabrina Tosi, Marcia Hall, and Emmanouil Karteris. 2021. "Preclinical Studies on the Effect of Rucaparib in Ovarian Cancer: Impact of BRCA2 Status" Cells 10, no. 9: 2434. https://doi.org/10.3390/cells10092434

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