Tranylcypromine - an antidepressant, shows promise as cancer treatment
Potential for retinoids to treat more common types of AML
A retinoid, all-trans retinoic acid (ATRA), which is a vitamin A-derivative, is already used successfully to treat a rare sub-type of acute myeloid leukaemia (AML). However this drug has not been effective for the more common types of AMLs. Team leader Arthur Zelent, PhD, and colleagues at The Institute of Cancer Research (ICR), UK have been working to unlock the potential of retinoids to treat other patients with AML. In a paper published in Nature Medicine on 11 March 2012, they show that the key could be an antidepressant tranylcypromine.
Until now, it has been a mystery why the other forms of AML don't respond to ATRA. This new study revealed that there is a molecular block that could be reversed with a second drug that is already commonly used as an antidepressant. According to UK researchers this is a very promising strategy, and if these findings can be replicated in patients the potential benefits will be enormous.
The team looked to an emerging area of research
ATRA works by encouraging the leukaemia 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 - 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 tranylcypromine, 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 has already started a phase II clinical trial of the drug combination in acute myeloid leukaemia patients.
Potential combination therapy uses drugs already available on the market
Both the retinoid ATRA and the antidepressant tranylcypromine are already available in the UK and off-patent, so these drugs should not be expensive for the health service. Importantly, the researchers believe these drugs are targeting only the cancer cells and leaving normal healthy cells largely untouched, so hopefully they would have fewer side-effects for patients than standard drugs. They look forward to seeing the results of the clinical trials.
The study was a collaboration between scientists at the ICR, Cardiff University and Queen's University, Belfast, in the UK; John Hopkins University, Baltimore, Progen Pharmaceuticals and Medical University of South Carolina in the USA; the University Health Network and the University of Toronto in Canada; and the University of Münster in Germany. It was funded in the UK by Leukaemia & Lymphoma Research along with the Samuel Waxman Cancer Research Foundation.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
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