Drug’s ‘double hit’ overcomes leukaemia resistance
Thursday 12 July 2012
A drug that uses a unique ‘double hit’ to kill leukaemia cells could be a potential new treatment for patients with acute myeloid leukaemia. The research, majority funded by Cancer Research UK, is published today in Leukaemia*.
Around 30 per cent of patients with AML have faults in the FLT3 gene, which are linked to more aggressive leukaemias and poor survival. While drugs that target these faults are available, the disease eventually builds resistance, leaving treatments ineffective.
To combat this, researchers at The Institute of Cancer Research (ICR) in London, funded by Cancer Research UK and Breakthrough Breast Cancer, developed a unique drug that targets AML cells in a “double hit”. The drug blocks the protein made by the faulty FLT3 gene along with another key protein – called Aurora kinase – which are both involved in driving cancer growth.
In healthy blood cells, FLT3 sends a signal to the cells telling them when to proliferate, while Aurora kinase plays a role in cell division. Leukaemia cells with faulty FLT3 can proliferate out of control, while many cancer cells have higher levels of Aurora kinase, causing errors during cell division. This ‘double hit’ drug blocks both mechanisms that otherwise promote leukaemia growth.
The drug is also unique because it can destroy cells even if they develop new faults in the FLT3 genes that would make them resistant to other inhibitors.
The combination led to complete remission in half of the mice treated with this drug, compared with only 25 per cent with an existing drug that only blocks FLT3.
Lead author Dr Spiros Linardopoulos, Leader of the Cancer Drug Target Discovery Team at The Institute of Cancer Research said: “There has been great interest in using FLT3 drugs to treat AML, but their effectiveness has been limited because leukaemia cells gain new mistakes in the FLT3 gene, causing resistance.
“Our new drug has the potential to overcome this and has a range of possible uses in AML – as a first line of attack for patients with faulty FLT3, in particular in those over 60 who don’t tolerate chemotherapy well, and also to treat leukaemia patients who have relapsed.”
Professor Paul Workman, director of the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research, said: “We’re excited about the potential of our new ‘double hit’ drug and are now planning to take it into clinical trials to see if it is effective in patients.”
The faults that occur in the FLT3 gene cause rapid cell division, and one particular mistake is linked to a very poor outcome in both adults and children with AML. Each year around 2,380 people are diagnosed with AML in the UK.
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “Cancer Research UK has a long history of developing drugs to treat leukaemia more effectively. But designing treatments that overcome resistance is a major challenge for researchers.
“By creating cells in the lab that mimic how drug resistance develops in AML the researchers were able to show that their new drug delivers a ‘double hit’ to halt cancer cells in their tracks. Next they will test the new drug in patients to see if it has the potential to treat people with aggressive AML.”
Media contact: Simon Shears in the Cancer Research UK press office on 020 3469 8054 or, out-of-hours, the duty press officer on 07050 264 059, or ICR Science Communications Manager Jane Bunce on 0207 153 5106
Notes to editors:
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. The Cancer Therapeutics Unit and Drug Development Unit at the ICR and The Royal Marsden were recently honoured with the 2012 American Association for Cancer Research Team Science Award for the “tremendous impact” of their preclinical and clinical studies.
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
Breakthrough Breast Cancer
• Breakthrough Breast Cancer’s vision is a future free from the fear of breast cancer.
• Breakthrough Breast Cancer is dedicated to improving and saving lives through finding the causes of breast cancer, enabling early detection, ensuring precise diagnosis, discovering new and better treatments and improving medical services.
• The charity funds ground-breaking research, campaign for better services and treatments and raise awareness of the signs and symptoms of breast cancer. Through this work the charity believes passionately that breast cancer can be beaten and the fear of the disease removed for good.
• Find more information go to breakthrough.org.uk
Cancer Research UK
- Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research
- The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.
- Cancer Research UK has been at the heart of the progress that has already seen survival rates in the UK double in the last forty years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.