2. Academic Validation
  3. High-throughput drug screening identifies novel therapeutics for Low Grade Serous Ovarian Carcinoma

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

  • Sci Data. 2024 Sep 19;11(1):1024. doi: 10.1038/s41597-024-03869-x.
Kathleen I Pishas 1 2,  Karla J Cowley 3,  Marta Llaurado-Fernandez 4 5,  Hannah Kim 4 5,  Jennii Luu 3,  Robert Vary 3,  Nikola A Bowden 6 7,  Ian G Campbell 1 2,  Mark S Carey 4 5,  Kaylene J Simpson # 8 9 10,  Dane Cheasley # 1 2
Affiliations

Affiliations

  • 1 Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
  • 2 The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
  • 3 Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
  • 4 Division of Gynecology Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, V5Z 1M9, Canada.
  • 5 Department of Clinical Research, BC Cancer, Vancouver, British Columbia, V5Z 4E6, Canada.
  • 6 School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
  • 7 Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton, New South Wales, 2305, Australia.
  • 8 The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia. [email protected].
  • 9 Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia. [email protected].
  • 10 Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, Victoria, 3010, Australia. [email protected].
  • # Contributed equally.
PMID: 39300112 DOI: 10.1038/s41597-024-03869-x
Abstract

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.

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