Slowing Cancers

UNC-TV Science: April 21, 2014
Cutting off Copper May Slow Several Cancers

Combating cancer could be as simple as limiting its supply of copper. A new study from Duke University and UNC - Chapel Hill found that a specific type of cancer requires copper ions to drive tumor growth. By limiting the cancer’s access to the metal, commonly found in pipes and wires, the researchers were able to limit the growth of tumors.

Apart from providing a convenient target for treatment, this discovery is significant because there are already FDA-approved drugs available to limit the body’s access to copper. Those drugs could greatly affect how quickly this research could be translated into a clinical treatment.

These copper-craving cancers come from a mutation in the BRAF gene. The BRAF gene is in the middle of a signaling pathway that tells cells when to multiply. When it works properly, it receives a signal from another gene and relays that signal to the cell. Mutated BRAF genes, however, can make their own signals, causing cells to multiply too quickly and thus creating tumors.

BRAF gene mutations cause several different cancers, including melanomas, thyroid, ovarian, colorectal and prostate tumors. Thus, the BRAF gene is an appealing target for treatment because it can help fight so many different cancers.

The study, led by Duke researcher Donita Brady, first identified that by adding copper to cells with BRAF gene mutations, the proteins that tell the cell to multiply became more active.

The team then modified those proteins so that they could no longer bind copper. This manipulation decreased tumor growth. The group also experimented with removing the proteins that scoop up copper and shuttle it around the cell. This also decreased the size and number of tumors.

The last experiment they performed involved attacking the copper itself with a drug called TTM. TTM is a chelate, and chelates don’t actually remove the metal they are meant to attack. They bind to the metal in more than one place, hold tight and prevent other things from binding to it. This decreases what is called the bioavailability of copper.

Imagine a cat playing with a small stuffed mouse. The cat lies on its back, sinks its claws into the mouse and curls up. Sure the mouse is still technically there, but good luck getting to it.

Chelates are old technology, and TTM is no exception. In fact, TTM is now commonly used to treat a genetic condition called Wilson disease, where copper piles up in patients’ livers and brains. Because doctors already treat patients with TTM, that greatly shortens the process that researchers need to go through to refine this research into a clinical treatment. In fact, Duke has been approved to do a clinical trial using TTM to treat melanoma, but enrollment hasn’t begun yet.

The study was published in the journal Nature.

- Daniel Lane

Daniel Lane covers science, medicine and the environment as a reporter/writer. He is currently pursuing a master's degree in medical and science journalism at UNC - Chapel Hill.