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Updated: Jun 25, 2025

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
VDX-111 targets proliferative pathways in canine cancer cell lines
Kristen B Farrell1, Sunetra Das1, Steven K Nordeen2
1Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, United States of America.
Abstract:
VDX-111 (also identified as AMPI-109) is a vitamin D derivative which has shown anticancer activity. To further assess the function of this compound against multiple cancer types, we examined the efficacy of VDX-111 against a panel of 30 well characterized canine cancer cell lines. Across a variety of cancer types, VDX-111 induced widely variable growth inhibition, cell death, and migration inhibition, at concentrations ranging from 10 nM to 1 μM. Growth inhibition sensitivity did not correlate strongly with tumor cell histotype; however, it was significantly correlated with the expression of genes in multiple cell signaling pathways, including the MAPK and PI3K-AKT pathways. We confirmed inhibition of these signaling pathways as likely participants in the effects of VDX-111. These results suggest that a subset of canine tumors may be sensitive to treatment with VDX-111, and suggests possible predictive markers of drug sensitivity and pharmacodynamic biomarkers of drug exposure that could be employed in future clinical trials.
Insights
VDX-111, a vitamin D derivative, shows anticancer activity in canine cancer cells. Its efficacy varies, correlating with cell signaling pathways like MAPK and PI3K-AKT, suggesting potential as a targeted therapy.
Area of Science:
- Oncology
- Pharmacology
- Veterinary Medicine
Background:
- Vitamin D derivatives are being explored for anticancer properties.
- VDX-111 (AMPI-109) is a novel vitamin D derivative with demonstrated anticancer activity.
- Canine cancer research provides a valuable model for comparative oncology.
Purpose of the Study:
- To evaluate the efficacy of VDX-111 against a diverse panel of canine cancer cell lines.
- To identify potential predictive markers for VDX-111 sensitivity.
- To investigate the molecular mechanisms underlying VDX-111's anticancer effects.
Main Methods:
- Testing VDX-111 on 30 characterized canine cancer cell lines.
- Assessing growth inhibition, cell death, and migration inhibition.
- Correlating drug sensitivity with gene expression in cell signaling pathways (MAPK, PI3K-AKT).
Main Results:
- VDX-111 demonstrated variable efficacy across different canine cancer types.
- Sensitivity to VDX-111 was significantly correlated with the expression of genes in the MAPK and PI3K-AKT pathways.
- Inhibition of these signaling pathways was confirmed as a likely mechanism of action.
Conclusions:
- A subset of canine tumors may be sensitive to VDX-111 treatment.
- Gene expression in MAPK and PI3K-AKT pathways may serve as predictive biomarkers for VDX-111 sensitivity.
- VDX-111 shows promise for future clinical trials in canine oncology.
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