Given that 90% of cancer-related deaths worldwide are due to metastasis and that current anti-cancer drugs do not target metastasis, we were driven to explore the underlying biology of this process. The failure of clinical candidates aimed at metastasis in clinical trials has raised valid concerns regarding the effectiveness of target-based therapies and our understanding of metastasis biology. To address this issue, we took a different approach. Our research focuses on a phenotypic and translational strategy, backed by prospective clinical samples, retrospective clinical trials and animal models. We identified critical steps in metastasis and selected a few potential targets. Using AI-based in silico modelling, we identified several FDA-approved drugs for non-oncology indications that bind to at least two of our identified targets. One such drug, MS-AP-030, approved for chronic hyperlipidaemia, was shown to delay metastasis onset.

We utilized our proprietary AI-ML platform, METSCAN®, to identify critical targets involved in metastasis. Next, we used AI-based protein-small molecule binding platforms to identify FDA-approved drugs, commonly applied for non-oncology purposes, that bind to at least two of these identified targets. These selected drugs were evaluated using our METAssay® platform to assess their anti-metastatic properties in colorectal cancer cell lines and primary colorectal cancer patient samples. Finally, the efficacy of MS-AP-030 was tested in animal models using the METVivo® platform.

In vitro studies were performed at non-cytotoxic concentrations. MS-AP-030, the most effective anti-metastatic compound, promoted epithelial-to-mesenchymal transition (EMT) and invasion—key steps in metastasis. Additionally, we observed increased reactive oxygen species (ROS) levels and elevated HIF-1α expression. Despite these effects, MS-AP-030 inhibited extravasation and blocked mesenchymal-to-epithelial transition and colony formation. In the Drosophila model, the compound significantly reduced metastasis with some impact on the primary tumour volume. Similar results were observed in the mice xenograft model, where MS-AP-030 treatment led to a notable reduction in lung and liver lesions.

Our findings suggest that MS-AP-030 promotes a mesenchymal phenotype to such an extent that the cells lose the ability to revert to an epithelial phenotype, ultimately preventing secondary site growth. We propose repositioning MS-AP-030 as a clinical candidate to delay metastasis in an adjuvant setting.