Epigenetic Compound Library Screen Identifies Ibrutinib as an Inhibitor of Ovarian Clear Cell Carcinoma Viability.

Ma, Y; Dickson, K-A; Sarker, FA; Alghalayini, A; Field, NR; Xie, T; Skipper, TS; Karafotias, A; Briscas, S; Yee, C; Ford, CE; Bowden, NA; Tran, N; Marsh, DJ

Epigenetic Compound Library Screen Identifies Ibrutinib as an Inhibitor of Ovarian Clear Cell Carcinoma Viability.

Ma, Y Dickson, K-A Sarker, FA

Alghalayini, A Field, NR

Xie, T Skipper, TS Karafotias, A Briscas, S Yee, C Ford, CE Bowden, NA Tran, N Marsh, DJ

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Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Cancer Medicine, 2026, 15, (4), pp. e71795
Issue Date:: 2026-04

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Field	Value	Language
dc.contributor.author	Ma, Y
dc.contributor.author	Dickson, K-A
dc.contributor.author	Sarker, FA https://orcid.org/0009-0003-0990-1796
dc.contributor.author	Alghalayini, A
dc.contributor.author	Field, NR https://orcid.org/0009-0004-6724-6360
dc.contributor.author	Xie, T
dc.contributor.author	Skipper, TS
dc.contributor.author	Karafotias, A
dc.contributor.author	Briscas, S
dc.contributor.author	Yee, C
dc.contributor.author	Ford, CE
dc.contributor.author	Bowden, NA
dc.contributor.author	Tran, N
dc.contributor.author	Marsh, DJ https://orcid.org/0000-0001-5899-4931
dc.date.accessioned	2026-04-10T01:14:32Z
dc.date.available	2026-03-30
dc.date.available	2026-04-10T01:14:32Z
dc.date.issued	2026-04
dc.identifier.citation	Cancer Medicine, 2026, 15, (4), pp. e71795
dc.identifier.issn	2045-7634
dc.identifier.issn	2045-7634
dc.identifier.uri	http://hdl.handle.net/10453/194628
dc.description.abstract	BACKGROUND: Ovarian clear cell carcinoma (OCCC) is an endometriosis-associated ovarian cancer subtype. Somatic mutations in OCCC are reported in ARID1A, PIK3CA, and the TERT promoter (TERTp), as well as less commonly in KRAS and TP53 among other genes. OCCC is typically resistant to standard-of-care chemotherapy, especially after relapse. While recent studies have seen favourable responses to immunotherapy, patients with OCCC face limited therapeutic options. METHODS: With the objective of discovering new drug treatments for OCCC, we screened OCCC (RMG-1, JHOC-5, OV207, OVISE, OVMANA, OVTOKO, and TOV-21G) and non-OCCC cell lines with a commercially available epigenetic drug compound library at two concentrations. Based on specified selection criteria, drugs were sought that preferentially inhibited viability of OCCC versus non-OCCC cells, with subsequent validation in 2D and 3D bioprinted models and exploration of a relevant signalling pathway. RESULTS: Taken together, OCCC cell lines were more sensitive to the Bruton's Tyrosine Kinase (BTK) inhibitor ibrutinib than non-OCCC cells, with some variation in response observed between cell lines in 2D and 3D bioprinted cultures. Furthermore, ibrutinib inhibited PI3K/AKT/mTOR cell survival signalling in some but not all OCCC cell lines, suggesting that this drug functions on additional pathways. CONCLUSIONS: Ibrutinib is used clinically to treat specific B cell disorders; however, it is not currently approved to treat solid tumours. Data presented in OCCC cell lines complements clinical observations of a therapeutic response to ibrutinib in low-grade serous ovarian cancer. Ibrutinib demonstrates potential for the treatment of certain rare subtypes of ovarian cancer and should be further investigated.
dc.description.sponsorship	National Health and Medical Research Council (2019296)
dc.format	Print
dc.language	eng
dc.publisher	Wiley
dc.relation	http://purl.org/au-research/grants/nhmrc/2019296
dc.relation.ispartof	Cancer Medicine
dc.relation.isbasedon	10.1002/cam4.71795
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1112 Oncology and Carcinogenesis
dc.subject.classification	3211 Oncology and carcinogenesis
dc.subject.mesh	Humans
dc.subject.mesh	Adenine
dc.subject.mesh	Female
dc.subject.mesh	Ovarian Neoplasms
dc.subject.mesh	Piperidines
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Adenocarcinoma, Clear Cell
dc.subject.mesh	Cell Survival
dc.subject.mesh	Epigenesis, Genetic
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Protein Kinase Inhibitors
dc.subject.mesh	Pyrimidines
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Drug Screening Assays, Antitumor
dc.subject.mesh	Pyrazoles
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Humans
dc.subject.mesh	Adenocarcinoma, Clear Cell
dc.subject.mesh	Ovarian Neoplasms
dc.subject.mesh	Piperidines
dc.subject.mesh	Pyrazoles
dc.subject.mesh	Pyrimidines
dc.subject.mesh	Adenine
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Protein Kinase Inhibitors
dc.subject.mesh	Drug Screening Assays, Antitumor
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Cell Survival
dc.subject.mesh	Epigenesis, Genetic
dc.subject.mesh	Female
dc.title	Epigenetic Compound Library Screen Identifies Ibrutinib as an Inhibitor of Ovarian Clear Cell Carcinoma Viability.
dc.type	Journal Article
utslib.citation.volume	15
utslib.location.activity	United States
utslib.for	0601 Biochemistry and Cell Biology
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/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Women & Children’s Health Research Collaborative (WCHC)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Health Technologies (CHT)
pubs.organisational-group	University of Technology Sydney/Faculty of Science/Science Related HDR Students
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2026-04-10T01:14:27Z
pubs.issue	4
pubs.publication-status	Published
pubs.volume	15
utslib.citation.issue	4

Abstract:

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is an endometriosis-associated ovarian cancer subtype. Somatic mutations in OCCC are reported in ARID1A, PIK3CA, and the TERT promoter (TERTp), as well as less commonly in KRAS and TP53 among other genes. OCCC is typically resistant to standard-of-care chemotherapy, especially after relapse. While recent studies have seen favourable responses to immunotherapy, patients with OCCC face limited therapeutic options. METHODS: With the objective of discovering new drug treatments for OCCC, we screened OCCC (RMG-1, JHOC-5, OV207, OVISE, OVMANA, OVTOKO, and TOV-21G) and non-OCCC cell lines with a commercially available epigenetic drug compound library at two concentrations. Based on specified selection criteria, drugs were sought that preferentially inhibited viability of OCCC versus non-OCCC cells, with subsequent validation in 2D and 3D bioprinted models and exploration of a relevant signalling pathway. RESULTS: Taken together, OCCC cell lines were more sensitive to the Bruton's Tyrosine Kinase (BTK) inhibitor ibrutinib than non-OCCC cells, with some variation in response observed between cell lines in 2D and 3D bioprinted cultures. Furthermore, ibrutinib inhibited PI3K/AKT/mTOR cell survival signalling in some but not all OCCC cell lines, suggesting that this drug functions on additional pathways. CONCLUSIONS: Ibrutinib is used clinically to treat specific B cell disorders; however, it is not currently approved to treat solid tumours. Data presented in OCCC cell lines complements clinical observations of a therapeutic response to ibrutinib in low-grade serous ovarian cancer. Ibrutinib demonstrates potential for the treatment of certain rare subtypes of ovarian cancer and should be further investigated.

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http://hdl.handle.net/10453/194628