# VDX-111 targets proliferative pathways in canine cancer cell lines

## TL;DR

VDX-111, a vitamin D derivative, shows anticancer effects in canine cancer cell lines by targeting key signaling pathways.

## Contribution

The study identifies specific signaling pathways targeted by VDX-111 and potential biomarkers for drug sensitivity in canine cancers.

## Key findings

- VDX-111 induced growth inhibition, cell death, and migration inhibition in canine cancer cell lines.
- Sensitivity to VDX-111 correlated with gene expression in MAPK and PI3K-AKT signaling pathways.
- The results suggest potential predictive markers for drug sensitivity and pharmacodynamic biomarkers for future clinical trials.

## 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.