Related Experiment Video
Updated: Jan 3, 2026
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer
Stephanie Annett1,2, Gillian Moore1, Amy Short2
1School of Pharmacy and Biomolecular Sciences, Irish Centre for Vascular Biology, Royal College of Surgeons Ireland, Dublin, Ireland.
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.
Insights
ALM201, a peptide targeting cancer stem cells (CSCs) and angiogenesis, showed efficacy in vascularized ovarian tumors. Its effectiveness is linked to FKBPL levels and low IL-6, suggesting a targeted therapeutic approach.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- ALM201 is a FKBPL-derived therapeutic peptide with prior oncology development.
- Completed Phase 1a clinical trial in ovarian cancer and advanced solid tumors.
Purpose of the Study:
- Evaluate ALM201's efficacy against cancer stem cells (CSCs) and its mechanisms of action.
- Investigate the role of FKBPL in high-grade serous ovarian cancer (HGSOC).
Main Methods:
- Utilized in vitro CSC assays and in vivo tumor models (xenografts).
- Employed immunohistochemistry, ELISA, qRT-PCR, RNAseq, and western blotting for mechanistic studies.
- Assessed endogenous FKBPL protein levels via tissue microarrays.
Main Results:
- ALM201 reduced CSCs by inducing differentiation in cell lines and patient samples.
- Disrupted angiogenesis and decreased CSCs in vascularized xenografts, causing tumor growth delay.
- Showed limited efficacy in non-vascularized tumors with high IL-6, linked to vasculogenic mimicry.
- High endogenous FKBPL correlated with improved progression-free interval in HGSOC.
Conclusions:
- FKBPL-based therapy offers dual targeting of angiogenesis and CSCs.
- ALM201 targets the CD44/STAT3 pathway.
- Effective in vascularized HGSOC with low IL-6.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
02:38Mitogens and the Cell Cycle