Beyond HRD Status: Unraveling Genetic Variants Impacting PARP Inhibitor Sensitivity in Advanced Ovarian Cancer

Maj K Kjeldsen; Morten Jørgensen; Dina Sofie B Grønseth; Martin Schønemann-Lund; Gitte-Bettina Nyvang; Charlotte Aaquist Haslund; Anja Oer Knudsen; Anne Krejbjerg Motavaf; Susanne Malander; Maarit Anttila; Gabriel Lindahl; Johanna Mäenpää; Maria Dimoula; Theresa L Werner; Trine Zeeberg Iversen; Sakari Hietanen; Lars Fokdal; Hanna Dahlstrand; Line Bjørge; Michael J Birrer; Mansoor R Mirza; Maria Rossing

doi:10.1158/2767-9764.CRC-24-0294

Beyond HRD Status: Unraveling Genetic Variants Impacting PARP Inhibitor Sensitivity in Advanced Ovarian Cancer

Cancer Res Commun. 2024 Dec 1;4(12):3190-3200. doi: 10.1158/2767-9764.CRC-24-0294.

Authors

Maj K Kjeldsen^{1

2

3}, Morten Jørgensen¹, Dina Sofie B Grønseth², Martin Schønemann-Lund⁴, Gitte-Bettina Nyvang^{3

5}, Charlotte Aaquist Haslund^{3

6}, Anja Oer Knudsen^{3

5}, Anne Krejbjerg Motavaf⁶, Susanne Malander^{3

7

8}, Maarit Anttila^{3

9}, Gabriel Lindahl^{3

10

11}, Johanna Mäenpää^{3

12}, Maria Dimoula^{3

13}, Theresa L Werner¹⁴, Trine Zeeberg Iversen^{3

15}, Sakari Hietanen^{3

16}, Lars Fokdal^{3

17}, Hanna Dahlstrand^{3

18}, Line Bjørge^{3

19

20}, Michael J Birrer²¹, Mansoor R Mirza^#^{1

3}, Maria Rossing^#^{2

22}

Affiliations

¹ Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
² Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
³ Nordic Society of Gynecological Oncology-Clinical Trial Unit (NSGO-CTU), Copenhagen, Denmark.
⁴ Department of Anesthesia and Intensive Care, Odense University Hospital, Odense, Denmark.
⁵ Department of Oncology, Odense University Hospital, Odense, Denmark.
⁶ Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
⁷ Department of Oncology, Skane University Hospital, Lund University, Lund, Sweden.
⁸ Department of Clinical Science, Skane University Hospital, Lund University, Lund, Sweden.
⁹ Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland.
¹⁰ Department of Oncology, Linköping University, Linköping, Sweden.
¹¹ Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
¹² Tampere University and Cancer Center, Tampere University Hospital, Tampere, Finland.
¹³ Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
¹⁴ Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
¹⁵ Department of Oncology, Herlev-Gentofte University Hospital, Herlev, Denmark.
¹⁶ Department of Obstetrics and Gynecology, Turku University Hospital and FICAN West, Turku, Finland.
¹⁷ Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Odense, Denmark.
¹⁸ Department of Oncology-Pathology, Karolinska Institutet and Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
¹⁹ Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
²⁰ Department of Clinical Science, Centre for Cancer Biomarkers CCBIO, University of Bergen, Bergen, Norway.
²¹ Winthrop P. Rockefeller Cancer Institute, Little Rock, Arkansas.
²² Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

^# Contributed equally.

Abstract

The irregular response to PARPi in HRD-positive and -negative tumors highlights the need for identifying additional biomarkers. This study explores the mutational landscape beyond HRD status in AOC, ultimately advancing precision oncology in future clinical practice.

MeSH terms

Adult
Aged
BRCA1 Protein / genetics
BRCA2 Protein / genetics
Biomarkers, Tumor / genetics
Drug Resistance, Neoplasm / genetics
Female
Humans
Middle Aged
Mutation*
Ovarian Neoplasms* / drug therapy
Ovarian Neoplasms* / genetics
Poly(ADP-ribose) Polymerase Inhibitors* / pharmacology
Poly(ADP-ribose) Polymerase Inhibitors* / therapeutic use

Substances

Poly(ADP-ribose) Polymerase Inhibitors
Biomarkers, Tumor
BRCA2 Protein
BRCA1 Protein
BRCA1 protein, human