Retinoids have already transformed one rare type of fatal leukemia into a curable disease
An antidepressant combined with a drug derived from vitamin A could be used to treat a common adult form of leukemia, according to laboratory research led by a team at The Institute of Cancer Research (ICR).
A retinoid called all-trans retinoic acid (ATRA), which is a vitamin A-derivative, is already used successfully to treat a rare sub-type of acute myeloid leukemia (AML) *, however this drug has not been effective for the more common types of AMLs.
Team leader Dr Arthur Zelent and colleagues at the ICR, with principal funding from leukemia & Lymphoma Research, have been working to unlock the potential of retinoids to treat other patients with AML. In a paper recenlty published in Nature Medicine, they show that the key could be an antidepressant called tranylcypromine (TCP).
“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,” senior author Dr Zelent, from the ICR, said. “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 works by encouraging the leukemia cells to mature and die naturally. The team thinks the failure of AML to respond to this drug may be due to genes that ATRA normally targets becoming switched off. In their search for a drug that could be used to reboot the activity of ATRA, the team looked to an emerging area of research called epigenetics. Epigenetic drugs do not target genes directly but instead target whether genes are switched on or off. They discovered that inhibiting an enzyme called LSD1, using TCP, could switch these genes on again and make the cancer cells susceptible to ATRA.
Along with collaborators at the University of Münster in Germany, the team have already started a Phase II clinical trial of the drug combination in acute myeloid leukemia patients.
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