Inhibition of c-FLIP alongside TRAIL treatment suppresses prostate cancer stem cell activity

Turnham, Daniel J. ORCID: https://orcid.org/0000-0002-2540-7363, French, Rhiannon, Frame, Fiona M., Meniel, Valerie S., Maitland, Norman J. and Clarkson, Richard W. E. ORCID: https://orcid.org/0000-0001-7389-8673 2026. Inhibition of c-FLIP alongside TRAIL treatment suppresses prostate cancer stem cell activity. British Journal of Cancer 10.1038/s41416-026-03359-4

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Abstract

Background: Prostate cancer is a leading cause of cancer-associated death in men worldwide. Inhibition of the Cellular FLICE-like Inhibitory Protein (cFLIP), which is overexpressed in prostate cancer, alongside TRAIL treatment can trigger apoptosis and suppress cancer stem cell (CSC) activity in different cancer types but has not been fully explored in prostate cancer. Methods: Established and primary prostate cancer lines were treated with the cFLIP inhibitor, OH14, in combination with recombinant TRAIL to investigate changes in viability and colony forming potential. Patient-derived xenograft (PDX) tumour cells were treated ex vivo and re-transplanted into mice in limiting dilution assays. Docetaxel resistant PC-3 cells were also treated with OH14 +/- docetaxel, while PDX tumours were treated in vivo with this combination. Results: Combined OH14 and TRAIL treatment induced a potent apoptotic response in prostate cancer cells, significantly reducing viability and CSC activity compared to single agents. OH14 also sensitised tumour cells to docetaxel both in vitro and in vivo. Conclusions: Inhibition of cFLIP in combination with either TRAIL or docetaxel has the potential to be used as a novel therapeutic approach to provide more potent, long-lasting benefits to men with prostate cancer.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine Schools > Biosciences
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	0007-0920
Date of First Compliant Deposit:	9 March 2026
Date of Acceptance:	10 February 2026
Last Modified:	09 Mar 2026 11:01
URI:	https://orca.cardiff.ac.uk/id/eprint/185583

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