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Herding cancer cells to their death
Date:6/20/2013

s to proliferate and to express a protein known as Tyrosinase that fuels pigment production. The scientists found that methotrexatea drug currently used to treat autoimmune diseases and some other cancers, though not melanomahad precisely that effect. The Spanish team then synthesized a novel molecule called TMECG that is lethal only when it is chemically modified by Tyrosinase. When activated by Tyrosinase, TMECG disrupts the protein machinery of cell division and so poisons cells that are multiplying rapidly.

"The beauty of the therapy," says Professor Jos Neptuno Rodriguez-Lpez, PhD, leader of the Spanish team at the University of Murcia, is that "TMECG is activated by a process that is specific to pigmented cells but not other cells. So, first the methotrexate sensitizes melanoma cells to the effects of TMECG. Then that molecule gets processed and activated by Tyrosinase to form an active compound that kills rapidly dividing cells. Even better, the methotrexate then delivers a second blow to melanoma cells by prompting them to commit suicide through a very specific mechanism."

The researchers found that the combined treatment efficiently destroyed melanoma cells in culture, even those derived from patient tumors resistant to vemurafenib and other targeted melanoma therapies. It also significantly suppressed tumors in one mouse model and diminished metastases in another.

In mice, the treatment combination does not appear to injure other pigmented cells, such as healthy cells of the skin, or those of the iris or the retina, probably because those cells are not rapidly proliferating. The researchers are now refining their new drug to improve its pharmacologic profile and figure out how to deliver it to the right places in the body.

"Think about what you ideally want from a cancer therapy," says Professor Colin Goding, PhD, Member of the Ludwig Institute for Cancer Research who is based at the University of Oxford. "You want a the
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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