Journal article

Small-scale mutations are infrequent as mechanisms of resistance in post-PARP inhibitor tumour samples in high grade serous ovarian cancer

Nikki L Burdett, Madelynne O Willis, Ahwan Pandey, Sian Fereday, Anna DeFazio, David DL Bowtell, Elizabeth L Christie, Nadia Traficante

Scientific Reports | Nature Portfolio | Published : 2023

DOI: 10.1038/s41598-023-48153-x

Abstract

While the introduction of poly-(ADP)-ribose polymerase (PARP) inhibitors in homologous recombination DNA repair (HR) deficient high grade serous ovarian, fallopian tube and primary peritoneal cancers (HGSC) has improved patient survival, resistance to PARP inhibitors frequently occurs. Preclinical and translational studies have identified multiple mechanisms of resistance; here we examined tumour samples collected from 26 women following treatment with PARP inhibitors as part of standard of care or their enrolment in clinical trials. Twenty-one had a germline or somatic BRCA1/2 mutation. We performed targeted sequencing of 63 genes involved in DNA repair processes or implicated in ovarian ca..

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University of Melbourne Researchers

Nikki Burdett Author

Julie Fereday Author

David Bowtell Author

Elizabeth Christie Author

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Grants

Awarded by NHMRC

Awarded by Victoria Cancer Agency

Funding Acknowledgements

This study was supported by NHMRC (APP1189939 & APP1161198) and the Victoria Cancer Agency MCRF21004 grants.

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Keywords

Clinical Research

5.1 Pharmaceuticals

3211 Oncology and Carcinogenesis

Somatic Mutations

31 Biological Sciences

Aocs Study Group

Science & Technology

Cancer Genomics

Prostate-Cancer

Germline Mutations

Genetic Testing

Homologous Recombination

Science & Technology - Other Topics

Brca2 Reversion Mutations

Multidisciplinary Sciences

Clinical Trials and Supportive Activities

2.1 Biological and Endogenous Factors

32 Biomedical and Clinical Sciences