Sunday 11 March 2012
An antidepressant combined with a drug derived from vitamin A could be used to treat a common adult form of leukaemia, 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 leukaemia (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 Leukaemia & Lymphoma Research, have been working to unlock the potential of retinoids to treat other patients with AML. In a paper published in Nature Medicine today, they show that the key could be an antidepressant called tranylcypromine (TCP).
“Retinoids have already transformed one rare type of fatal leukaemia into a curable disease. We’ve now found a way to harness these powerful drugs to treat far more common types of leukaemia,” 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 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 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 leukaemia patients.
Co-author Dr Kevin Petrie 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.”
Each year, more than 2,200 people in the UK are diagnosed with acute myeloid leukaemia, a type of cancer characterised by the uncontrolled growth of immature white blood cells in the bone marrow.
Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said: “These results are extremely significant. Current drugs for AML are very aggressive and many older patients have a poor outlook as they cannot tolerate treatment. ATRA has been a major success story in recent years in treating a particular subtype of AML. In finding a way to expand its use, we would have the potential to save thousands of lives a year.”
The study was a collaboration between scientists at the ICR, Cardiff University and Queen’s University, Belfast, in the UK; Johns Hopkins University, Baltimore, Progen Pharmaceuticals and Medical University of South Carolina in the US; 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.
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Media Contact: ICR Science Communications Manager Jane Bunce on 0207 153 5106 or after hours 077217 47900
Notes to editors:
* Retinoids are already licensed to treat a type of AML called acute promyelocytic leukaemia (APL).
Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia with first author Tino Schenk from the ICR publishes in Nature Medicine on 11 March 2012.
The Institute of Cancer Research (ICR) is one of the world’s most influential cancer research institutes.
Scientists and clinicians at the ICR are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.
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.
As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR’s mission is to make the discoveries that defeat cancer. For more information visit www.icr.ac.uk
Leukaemia & Lymphoma Research is the only UK charity solely dedicated to research into blood cancers, including leukaemia, lymphoma and myeloma. Around 30,000 people of all ages, from children and teenagers to adults are diagnosed with a blood cancer in the UK every year.
We receive no government funding and rely entirely on voluntary support. In the next five years we need to raise £120 million to continue our lifesaving research. Further information, including patient information booklets, is available from beatingbloodcancers.org.uk or on 020 7405 0101.
The Samuel Waxman Cancer Research Foundation
The Samuel Waxman Cancer Research Foundation is an international organization dedicated to curing and preventing cancer. The Foundation is a pioneer in cancer research, focusing on uncovering the causes of cancer and reprogramming cancer cells.
We dedicate ourselves to delivering tailored, minimally toxic treatments to patients. Our mission is to eradicate cancer by bridging the gap between lab science and the patient.
Through our collaborative group of world-class scientists, the Institute Without Walls, investigators share information and tools to speed the pace of cancer research. Since our inception in 1976, the Foundation has awarded more than $75 million to support the work of nearly 200 researchers across the globe.
The University of Münster
With around 37,000 students the Westfälische Wilhelms-Universität (WWU) in Münster is the fourth-largest university in Germany. The teaching offered by its 15 departments comprises 250 courses in 110 subjects from practically every field of the Humanities, Social Sciences, Medicine and Natural Sciences.
The WWU is distinguished by outstanding research in many areas. In addition to targeted funding for top-level research, one focus is on junior academics. At the same time WWU provides for a wide range of research as the basis for helping further disciplinary excellence and interdisciplinary collaboration to grow.
Münster University is well placed in the international academic environment and is constantly extending this position. Internationalisation in the sense of increasingly international orientation and global networking is embedded in the University’s overall strategy and is a cross-disciplinary approach affecting all areas of the University – studying, teaching, research, administration and services.
For more Information visit http://www.uni-muenster.de/en/