March 13, 2012

Antidepressant May Treat Some Cancers

In trying to unlock the potential of retinoids to treat patients with acute myeloid leukemia (AML), scientists have found the antidepressant called tranylcypromine (TCP) may be the key.

Many types of AML can be treated with the retinoid all-trans retinoic acid (ATRA), a vitamin A-derivative. However, ATRA has not been shown to be effective with the more common types of AML.

Arthur Zelent, PhD and his team at the Institute of Cancer Research (ICR) have been studying TCP to unlock the potential to combat AML with these specific retinoids. They listed their findings in a paper published in Nature Medicine on March 11, 2012.

Speaking to Nature Medicine, senior author Dr Zelent said “Retinoids have already transformed one rare type of fatal leukemia into a curable disease. We´ve now found a way to harness these powerful drugs to treat far more common types of leukemia. Until now, it´s been a mystery why the other forms of AML don´t respond to this drug. Our study revealed that there was a molecular block that could be reversed with a second drug that is already commonly used as an antidepressant. We think this is a very promising strategy, and if these findings can be replicated in patients the potential benefits are enormous.”

ATRA, the drug commonly used to treat most cases of AML, works by encouraging the leukemia cells to mature quickly and then die. Zelent´s team thinks this drug isn´t effective on some cases of AML because of the genes that ATRA normally targets are being turned off.

The team decided to look into the emerging area of study called epigenetics. Epigenetic drugs look to turn genes on or off, rather than directly targeting specific genes. By using epigenetics, the team found that when used in tandem, TCP was able to turn off an enzyme called LSD1, thus making the cancer cells more susceptible to ATRA.

The team has already started phase II clinical trials of this drug combination to treat patients with AML along with collaborators at the University of Münster in Germany.

The research team´s findings  are a positive step forward in treating patients with AML. In addition to working together to effectively knock out AML cancer cells, these drugs do not target healthy cells, leaving the patients less susceptible to unpleasant side-effects.

Co-author Kevin Petrie, Ph.D., from the ICR says, “Both the retinoid ATRA and the antidepressant TCP are already available in the UK and off-patent, so these drugs should not be expensive for the health service. AML remains very difficult to treat and sadly is often fatal, with rates of the disease projected to increase significantly as the population ages, so it is particularly pleasing to have identified this new treatment approach. Importantly, we believe these drugs are targeting only the cancer cells and leaving normal healthy cells largely untouched, so we are hopeful that they would have fewer side-effects for patients than standard drugs. We look forward to seeing the results of the clinical trials.”


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