Ammonium Tetrathiomolybdate

 

Ammonium tetrathiomolybdate, called TM for short, is a drug initially developed to treat Wilson’s disease, a disorder where excess copper accumulates in the body. The body needs some copper, but excess copper as seen in Wilson’s disease causes significant problems unless it is chelated. Chelation of a substance, such as a metal, allows it to be appropriately eliminated from the body. As we see with many drugs, the patent on ammonium tetrathiomolybdate ran out and newer drugs were created which supplanted it. The result is that TM was mostly forgotten about.

Copper and Cancer

However, research has since uncovered the role of copper in angiogenesis––the formation of new blood vessels to supply cancer with nutrients and other resources needed for it to grow. We know that angiogenesis is one of the hallmarks of cancer. It turns out that copper is required for angiogenesis, and if we reduce the amount of copper available in the body, cancer will be deprived of a very important substrate.

In addition to lowering copper, TM also reduces blood levels of other substances needed by cancer to grow, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), interleukin-6 (IL-6), and interleukin-8 (IL-8). There are also studies suggesting that TM improves the effectiveness of various chemotherapy agents.

Incorporating Ammonium Tetrathiomolybdate into Treatment

We routinely check a blood level of copper, known as ceruloplasmin, on every patient. We have found that ceruloplasmin is almost always elevated, or at least in the high-normal range, when cancer is present. The use of ammonium tetrathiomolybdate as an off-label agent in cancer, with the express purpose of chelating copper, allows us to reduce copper to a much safer level. The “sweet spot” is a copper level low enough that we are preventing or greatly reducing angiogenesis, but not quite to zero since the body does need some copper for normal cellular processes.

Because it is no longer commercially available, TM must be compounded by a compounding pharmacy with expertise in it. Since it is also a weak chelator of iron, iron levels in the body should be monitored regularly. However, it is a very safe and well-tolerated drug which can be taken long-term.