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Article

Zebrafish Xenografts Unveil Sensitivity to Olaparib beyond BRCA Status

1
Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal
2
Institute for Research on Cancer and Aging of Nice (IRCAN), Université Côte d’Azur, U1081 UMR7284 UNS, 06107 Nice, France
*
Author to whom correspondence should be addressed.
These authors contributed equally for this work.
Cancers 2020, 12(7), 1769; https://doi.org/10.3390/cancers12071769
Received: 6 May 2020 / Revised: 11 June 2020 / Accepted: 29 June 2020 / Published: 2 July 2020
Poly (ADP-ribose) polymerase (PARP) inhibition in BRCA-mutated cells results in an incapacity to repair DNA damage, leading to cell death caused by synthetic lethality. Within the treatment options for advanced triple negative breast cancer, the PARP inhibitor olaparib is only given to patients with BRCA1/2 mutations. However, these patients may show resistance to this drug and BRCA1/2 wild-type tumors can show a striking sensitivity, making BRCA status a poor biomarker for treatment choice. Aiming to investigate if the zebrafish model can discriminate sensitivities to olaparib, we developed zebrafish xenografts with different BRCA status and measured tumor response to treatment, as well as its impact on angiogenesis and metastasis. When challenged with olaparib, xenografts revealed sensitivity phenotypes independent of BRCA. Moreover, its combination with ionizing radiation increased the cytotoxic effects, showing potential as a combinatorial regimen. In conclusion, we show that the zebrafish xenograft model may be used as a sensitivity profiling platform for olaparib in monotherapy or in combinatorial regimens. Hence, this model presents as a promising option for the future establishment of patient-derived xenografts for personalized medicine approaches beyond BRCA status. View Full-Text
Keywords: breast cancer; BRCA1/2; ionizing radiation; olaparib; PARP; radiotherapy; xenografts; zebrafish breast cancer; BRCA1/2; ionizing radiation; olaparib; PARP; radiotherapy; xenografts; zebrafish
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MDPI and ACS Style

Varanda, A.B.; Martins-Logrado, A.; Godinho Ferreira, M.; Fior, R. Zebrafish Xenografts Unveil Sensitivity to Olaparib beyond BRCA Status. Cancers 2020, 12, 1769. https://doi.org/10.3390/cancers12071769

AMA Style

Varanda AB, Martins-Logrado A, Godinho Ferreira M, Fior R. Zebrafish Xenografts Unveil Sensitivity to Olaparib beyond BRCA Status. Cancers. 2020; 12(7):1769. https://doi.org/10.3390/cancers12071769

Chicago/Turabian Style

Varanda, Ana B., Ana Martins-Logrado, Miguel Godinho Ferreira, and Rita Fior. 2020. "Zebrafish Xenografts Unveil Sensitivity to Olaparib beyond BRCA Status" Cancers 12, no. 7: 1769. https://doi.org/10.3390/cancers12071769

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