Abstract | BACKGROUND: Low grade serous ovarian carcinoma (LGSOC) is a distinct histotype of ovarian cancer characterised high levels of intrinsic chemoresistance, highlighting the urgent need for new treatments. High throughput screening in clinically-informative cell-based models represents an attractive strategy for identifying candidate treatment options for prioritisation in clinical studies. METHODS: We performed a high throughput drug screen of 1610 agents across a panel of 6 LGSOC cell lines (3 RAS/RAF-mutant, 3 RAS/RAF-wildtype) to identify novel candidate therapeutic approaches. Validation comprised dose-response analysis across 9 LGSOC models and 5 high grade serous comparator lines. RESULTS: CONCLUSION:
Dasatinib and other SFK inhibitors represent novel candidate treatments for LGSOC and demonstrate synergy with trametinib. Disulfiram represents an additional treatment strategy worthy of investigation.
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Authors | Robert L Hollis, Richard Elliott, John C Dawson, Narthana Ilenkovan, Rosie M Matthews, Lorna J Stillie, Ailsa J Oswald, Hannah Kim, Marta Llaurado Fernandez, Michael Churchman, Joanna M Porter, Patricia Roxburgh, Asier Unciti-Broceta, David M Gershenson, C Simon Herrington, Mark S Carey, Neil O Carragher, Charlie Gourley |
Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 186
Pg. 42-52
(Apr 05 2024)
ISSN: 1095-6859 [Electronic] United States |
PMID | 38582027
(Publication Type: Journal Article)
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Copyright | Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. |