Zebrafish Xenografts Unveil Sensitivity to Olaparib beyond BRCA Status.
BRCA1/2
PARP
breast cancer
ionizing radiation
olaparib
radiotherapy
xenografts
zebrafish
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
02 Jul 2020
02 Jul 2020
Historique:
received:
06
05
2020
revised:
11
06
2020
accepted:
29
06
2020
entrez:
8
7
2020
pubmed:
8
7
2020
medline:
8
7
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32630796
pii: cancers12071769
doi: 10.3390/cancers12071769
pmc: PMC7408583
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Fundação Champalimaud
ID : 168
Organisme : Fundação para a Ciência e a Tecnologia
ID : FCT-PTDC/MEC-ONC/31627/2017
Organisme : Fundação para a Ciência e a Tecnologia
ID : Congento (LISBOA-01-0145-FEDER-022170
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