FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer.
Ontology highlight
ABSTRACT: Background
ALM201 is a therapeutic peptide derived from FKBPL that has previously undergone preclinical and clinical development for oncology indications and has completed a Phase 1a clinical trial in ovarian cancer patients and other advanced solid tumours.Methods
In vitro, cancer stem cell (CSC) assays in a range of HGSOC cell lines and patient samples, and in vivo tumour initiation, growth delay and limiting dilution assays, were utilised. Mechanisms were determined by using immunohistochemistry, ELISA, qRT-PCR, RNAseq and western blotting. Endogenous FKBPL protein levels were evaluated using tissue microarrays (TMA).Results
ALM201 reduced CSCs in cell lines and primary samples by inducing differentiation. ALM201 treatment of highly vascularised Kuramochi xenografts resulted in tumour growth delay by disruption of angiogenesis and a ten-fold decrease in the CSC population. In contrast, ALM201 failed to elicit a strong antitumour response in non-vascularised OVCAR3 xenografts, due to high levels of IL-6 and vasculogenic mimicry. High endogenous tumour expression of FKBPL was associated with an increased progression-free interval, supporting the protective role of FKBPL in HGSOC.Conclusion
FKBPL-based therapy can (i) dually target angiogenesis and CSCs, (ii) target the CD44/STAT3 pathway in tumours and (iii) is effective in highly vascularised HGSOC tumours with low levels of IL-6.
SUBMITTER: Annett S
PROVIDER: S-EPMC7000737 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer.
Annett Stephanie S Moore Gillian G Short Amy A Marshall Andrea A McCrudden Cian C Yakkundi Anita A Das Sudipto S McCluggage W Glenn WG Nelson Laura L Harley Ian I Moustafa Nermeen N Kennedy Catherine J CJ deFazio Anna A Brand Alison A Sharma Raghwa R Brennan Donal D O'Toole Sharon S O'Leary John J Bates Mark M O'Riain Ciarán C O'Connor Darran D Furlong Fiona F McCarthy Helen H Kissenpfennig Adrien A McClements Lana L Robson Tracy T
British journal of cancer 20191127 3
<h4>Background</h4>ALM201 is a therapeutic peptide derived from FKBPL that has previously undergone preclinical and clinical development for oncology indications and has completed a Phase 1a clinical trial in ovarian cancer patients and other advanced solid tumours.<h4>Methods</h4>In vitro, cancer stem cell (CSC) assays in a range of HGSOC cell lines and patient samples, and in vivo tumour initiation, growth delay and limiting dilution assays, were utilised. Mechanisms were determined by using i ...[more]
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