Antidepressant could help the workings of anticancer drug used in leukemia

By Dr. Ananya Mandal, MDMar 13 2012

A new study shows that an antidepressant could be crucial in helping cancer treatment drugs reach their full potential.

The study by scientists at the Institute of Cancer Research found that tranylcypromine (TCP) – which can be used to treat psychotic depressive states - can make cancer cells vulnerable to the effects of a vitamin A-derivative drug called ATRA.

Retinoids are a class of chemical compounds related chemically to vitamin A. ATRA is already used successfully to treat a rare form of acute myeloid leukemia (AML), but up until now, has not been effective against other types of the disease. ATRA works by encouraging leukemia cells to mature and die naturally, but the researchers say that the reason many AML patients do not respond to the treatment is because the genes that ATRA normally attacks are switched off by an enzyme called LSD1. The scientists discovered that using TCP to block this 'off switch' could reactivate these genes, making the cancer cells susceptible to ATRA.

“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 leukaemia. 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,” said team leader Dr Arthur Zelent, from the ICR. “We think this is a very promising strategy and if these findings can be replicated in patients the potential benefits are enormous,” said Zelent.

Around 2,000 people are diagnosed with AML each year and, while it can affect people of any age, it is more common in the over 65s.

The team has already joined forces with the University of Munster in Germany to start a Phase II clinical trial of the drug combination in AML patients. The authors also commented that 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.

Martin Ledwick, head information Nurse at Cancer Research UK, said that it was exciting to see new approaches to treatment for AML being developed, “Not all AML patients are suitable for treatments like chemotherapy and bone marrow transplants, and these therapies can be hard to cope with. This trial is especially interesting as it helps to explain why a treatment that works in a rare form of AML doesn't work in other types and attempts to get over this problem.”

But he cautioned that further research will need to be done to see whether the laboratory results really do improve things for patients with AML.