High-throughput drug screening identifies novel therapeutics for Low Grade Serous Ovarian Carcinoma.

Humans Female Ovarian Neoplasms / drug therapy High-Throughput Screening Assays Cystadenocarcinoma, Serous / drug therapy Cell Line, Tumor Drug Screening Assays, Antitumor Antineoplastic Agents / pharmacology Carcinoma, Ovarian Epithelial / drug therapy

Journal

Scientific data
ISSN: 2052-4463
Titre abrégé: Sci Data
Pays: England
ID NLM: 101640192

Informations de publication

Date de publication:
19 Sep 2024
Historique:
received: 18 03 2024
accepted: 06 09 2024
medline: 20 9 2024
pubmed: 20 9 2024
entrez: 19 9 2024
Statut: epublish

Résumé

Low grade serous carcinoma (LGSOC) is a rare epithelial ovarian cancer with unique molecular characteristics compared to the more common tubo-ovarian high-grade serous ovarian carcinoma. Pivotal clinical trials guiding the management of epithelial ovarian cancer lack sufficient cases of LGSOC for meaningful subgroup analysis, hence overall findings cannot be extrapolated to rarer chemo-resistant subtypes such as LGSOC. Furthermore, there is a need for more effective therapies for the treatment of relapsed disease, as treatment options are limited. To address this, we conducted the largest quantitative high-throughput drug screening effort (n = 3436 compounds) in 12 patient-derived LGSOC cell lines and one normal ovary cell line to identify unexplored therapeutic avenues. Using a combination of high-throughput robotics, high-content imaging and novel data analysis pipelines, our data set identified 60 high and 19 moderate confidence hits which induced cancer cell specific cytotoxicity at the lowest compound dose assessed (0.1 µM). We also revealed a series of known (mTOR/PI3K/AKT) and novel (EGFR and MDM2-p53) drug classes in which LGSOC cell lines showed demonstrable susceptibility to.

Identifiants

DOI: 10.1038/s41597-024-03869-x PMID: 39300112
pubmed: 39300112
doi: 10.1038/s41597-024-03869-x
pii: 10.1038/s41597-024-03869-x
doi:

Substances chimiques

Antineoplastic Agents 0

Types de publication

Journal Article Dataset

Langues

eng

Sous-ensembles de citation

IM

Pagination

1024

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Kathleen I Pishas (KI)

Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia.

Karla J Cowley (KJ)

Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.

Marta Llaurado-Fernandez (M)

Division of Gynecology Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, V5Z 1M9, Canada.
Department of Clinical Research, BC Cancer, Vancouver, British Columbia, V5Z 4E6, Canada.

Hannah Kim (H)

Division of Gynecology Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, V5Z 1M9, Canada.
Department of Clinical Research, BC Cancer, Vancouver, British Columbia, V5Z 4E6, Canada.

Jennii Luu (J)

Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.

Robert Vary (R)

Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.

Nikola A Bowden (NA)

School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton, New South Wales, 2305, Australia.

Ian G Campbell (IG)

Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
ORCID: 0000-0002-7773-4155

Mark S Carey (MS)

Division of Gynecology Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, V5Z 1M9, Canada.
Department of Clinical Research, BC Cancer, Vancouver, British Columbia, V5Z 4E6, Canada.

Kaylene J Simpson (KJ)

The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia. kaylene.simpson@petermac.org.
Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia. kaylene.simpson@petermac.org.
Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, Victoria, 3010, Australia. kaylene.simpson@petermac.org.

Dane Cheasley (D)

Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › High-throughput drug screening identifies...
questionsmedicales.fr › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Tumeurs de l'ovaire › High-throughput drug screening identifies...
questionsmedicales.fr › Techniques d'investigation › Tests de criblage à haut débit › High-throughput drug screening identifies...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Tumeurs kystiques, mucineuses et séreuses › Cystadénocarcinome › Cystadénocarcinome séreux › High-throughput drug screening identifies...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › High-throughput drug screening identifies...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de criblage d'agents antitumoraux › High-throughput drug screening identifies...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › High-throughput drug screening identifies...
questionsmedicales.fr › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Tumeurs de l'ovaire › Carcinome épithélial de l'ovaire › High-throughput drug screening identifies...