Targeting Homologous Recombination Deficiency in Ovarian Cancer with PARP Inhibitors: Synthetic Lethal Strategies That Impact Overall Survival

Xie, T; Dickson, K-A; Yee, C; Ma, Y; Ford, CE; Bowden, NA; Marsh, DJ

Targeting Homologous Recombination Deficiency in Ovarian Cancer with PARP Inhibitors: Synthetic Lethal Strategies That Impact Overall Survival

Xie, T Dickson, K-A Yee, C Ma, Y Ford, CE Bowden, NA Marsh, DJ

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Publisher:: MDPI AG
Publication Type:: Journal Article
Citation:: Cancers, 2022, 14, (19), pp. 4621
Issue Date:: 2022-09-23

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Field	Value	Language
dc.contributor.author	Xie, T
dc.contributor.author	Dickson, K-A
dc.contributor.author	Yee, C
dc.contributor.author	Ma, Y
dc.contributor.author	Ford, CE
dc.contributor.author	Bowden, NA
dc.contributor.author	Marsh, DJ
dc.date.accessioned	2022-10-03T00:27:32Z
dc.date.available	2022-10-03T00:27:32Z
dc.date.issued	2022-09-23
dc.identifier.citation	Cancers, 2022, 14, (19), pp. 4621
dc.identifier.issn	2072-6694
dc.identifier.issn	2072-6694
dc.identifier.uri	http://hdl.handle.net/10453/162215
dc.description.abstract	<jats:p>The advent of molecular targeted therapies has made a significant impact on survival of women with ovarian cancer who have defects in homologous recombination repair (HRR). High-grade serous ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer, with over 50% displaying defective HRR. Poly ADP ribose polymerases (PARPs) are a family of enzymes that catalyse the transfer of ADP-ribose to target proteins, functioning in fundamental cellular processes including transcription, chromatin remodelling and DNA repair. In cells with deficient HRR, PARP inhibitors (PARPis) cause synthetic lethality leading to cell death. Despite the major advances that PARPis have heralded for women with ovarian cancer, questions and challenges remain, including: can the benefits of PARPis be brought to a wider range of women with ovarian cancer; can other drugs in clinical use function in a similar way or with greater efficacy than currently clinically approved PARPis; what can we learn from long-term responders to PARPis; can PARPis sensitise ovarian cancer cells to immunotherapy; and can synthetic lethal strategies be employed more broadly to develop new therapies for women with ovarian cancer. We examine these, and other, questions with focus on improving outcomes for women with ovarian cancer.</jats:p>
dc.language	en
dc.publisher	MDPI AG
dc.relation	Medical Research Future FundAPP1199620
dc.relation.ispartof	Cancers
dc.relation.isbasedon	10.3390/cancers14194621
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1112 Oncology and Carcinogenesis
dc.title	Targeting Homologous Recombination Deficiency in Ovarian Cancer with PARP Inhibitors: Synthetic Lethal Strategies That Impact Overall Survival
dc.type	Journal Article
utslib.citation.volume	14
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2022-10-03T00:27:30Z
pubs.issue	19
pubs.publication-status	Published online
pubs.volume	14
utslib.citation.issue	19

Abstract:

The advent of molecular targeted therapies has made a significant impact on survival of women with ovarian cancer who have defects in homologous recombination repair (HRR). High-grade serous ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer, with over 50% displaying defective HRR. Poly ADP ribose polymerases (PARPs) are a family of enzymes that catalyse the transfer of ADP-ribose to target proteins, functioning in fundamental cellular processes including transcription, chromatin remodelling and DNA repair. In cells with deficient HRR, PARP inhibitors (PARPis) cause synthetic lethality leading to cell death. Despite the major advances that PARPis have heralded for women with ovarian cancer, questions and challenges remain, including: can the benefits of PARPis be brought to a wider range of women with ovarian cancer; can other drugs in clinical use function in a similar way or with greater efficacy than currently clinically approved PARPis; what can we learn from long-term responders to PARPis; can PARPis sensitise ovarian cancer cells to immunotherapy; and can synthetic lethal strategies be employed more broadly to develop new therapies for women with ovarian cancer. We examine these, and other, questions with focus on improving outcomes for women with ovarian cancer.

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http://hdl.handle.net/10453/162215