Description: <p>Tetrathiomolybdate, often abbreviated TM, is a copper-chelating / copper-depleting agent. In cancer, it is mainly studied as an anti-angiogenic, anti-metastatic, tumor-microenvironment-modifying compound rather than as a conventional cytotoxic chemotherapy.<br>
TM → copper depletion ↓ → angiogenesis ↓ / endothelial progenitor cells ↓ / LOX-family activity ↓ / SOD1 activity ↓ → metastasis support ↓<br>
Tetrathiomolybdate binds copper and reduces biologically available copper.
</p>
<table>
<thead>
<tr>
<th>Pathway / target</th>
<th>Effect of tetrathiomolybdate</th>
<th>Cancer relevance</th>
<th>Notes</th>
</tr>
</thead>
<tbody>
<tr>
<td>Copper bioavailability</td>
<td>Decreases</td>
<td>Anti-cancer</td>
<td>TM binds copper and lowers biologically available copper needed by tumor-supporting enzymes.</td>
</tr>
<tr>
<td>Angiogenesis</td>
<td>Decreases</td>
<td>Anti-cancer</td>
<td>Copper depletion reduces angiogenic support and may limit tumor vascularization.</td>
</tr>
<tr>
<td>Endothelial progenitor cells</td>
<td>Decreases</td>
<td>Anti-metastatic</td>
<td>Relevant to high-risk breast cancer recurrence / tumor-microenvironment studies.</td>
</tr>
<tr>
<td>LOX / ECM remodeling</td>
<td>Likely decreases through copper depletion</td>
<td>Anti-invasive / anti-metastatic</td>
<td>LOX-family enzymes are copper-dependent and contribute to extracellular-matrix remodeling and metastatic niche formation.</td>
</tr>
<tr>
<td>SOD1</td>
<td>Decreases, especially with ATN-224</td>
<td>Can increase tumor oxidative stress vulnerability</td>
<td>This makes TM redox-active rather than a simple antioxidant.</td>
</tr>
<tr>
<td>Tumor dormancy</td>
<td>May promote / maintain</td>
<td>Potential anti-recurrence effect</td>
<td>Most relevant where microscopic residual disease remains after standard therapy.</td>
</tr>
<tr>
<td>Gross tumor shrinkage</td>
<td>Usually limited as monotherapy</td>
<td>Weak direct cytotoxic effect</td>
<td>Clinical signal appears stronger for stabilization or recurrence prevention than for tumor regression.</td>
</tr>
</tbody>
</table>