PALB2 or BARD1 loss confers homologous recombination deficiency and PARP inhibitor sensitivity in prostate cancer.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
29 Jun 2022
29 Jun 2022
Historique:
received:
17
09
2021
accepted:
08
06
2022
entrez:
29
6
2022
pubmed:
30
6
2022
medline:
30
6
2022
Statut:
epublish
Résumé
PARP inhibitors were recently approved for treatment of molecularly-defined subsets of metastatic castrate-resistant prostate cancer (mCRPC) patients. Although the PARP inhibitor olaparib was approved for use in patients with a mutation in one of fourteen genes, the mutation frequency of the genes varies widely in mCRPC and the impact of the less commonly altered genes on PARP inhibitor sensitivity is uncertain. We used functional approaches to directly test the impact of PALB2 and BARD1 loss on homologous recombination (HR) function and PARP inhibitor sensitivity in prostate cancer cell lines. PALB2 or BARD1 loss led to decreased HR function as measured by loss of radiation-induced Rad51 foci formation as well as decreased HR capacity in a cell-based reporter assay. PALB2 or BARD1 loss also significantly increased sensitivity to the PARP inhibitors olaparib and rucaparib across a panel of prostate cancer cell lines. These data support PALB2 and BARD1 loss as markers of clinically relevant PARP inhibitor sensitivity and highlight the potential to use functional approaches to complement and extend findings from clinical trials of targeted agents.
Identifiants
pubmed: 35768576
doi: 10.1038/s41698-022-00291-7
pii: 10.1038/s41698-022-00291-7
pmc: PMC9242979
doi:
Types de publication
Journal Article
Langues
eng
Pagination
49Subventions
Organisme : NCI NIH HHS
ID : K08 CA219504
Pays : United States
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : PC190196
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : W81XWH-18-2-0056
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : CA219504
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : CA228696
Organisme : NCI NIH HHS
ID : P01 CA228696
Pays : United States
Informations de copyright
© 2022. The Author(s).
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