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Scientists unravel cause of second cancer arising from targeted treatment



Wednesday 18 January 2012



Scientists at The Institute of Cancer Research (ICR) have shown how to prevent new cancers which can occur when malignant melanoma patients are treated with drugs known as BRAF inhibitors, in a Cancer Research UK-funded study published today in the New England Journal of Medicine. 


Previously, doctors had noticed that between 15 and 30 per cent of patients treated with BRAF inhibitors - including the FDA-approved vemurafenib (Zelboraf) - developed another type of skin cancer called cutaneous squamous cell carcinoma, which had to be removed surgically.  


Professor Richard Marais from the ICR and his collaborators from around the world examined squamous cell carcinoma tissue taken from 21 malignant melanoma patients who had been treated with vemurafenib in a clinical trial. They scanned the DNA of these new tumours for the presence of known cancer-causing mutations including HRAS, KRAS, NRAS, CDKN2A and TP53. Sixty per cent of the samples harboured mutations in either HRAS or KRAS.


Further testing demonstrated that the BRAF inhibitors do not directly trigger squamous cell carcinomas, rather they accelerate the development of existing cancerous changes to the skin that were not yet showing symptoms. Importantly, in mice they discovered that another type of drug – called a MEK inhibitor – could block the development of these second tumours even in the presence of the BRAF drugs.


Co-senior author Professor Marais says: “Around half of all patients with malignant melanoma have a mutation in their BRAF gene, and can be treated with BRAF-inhibiting drugs. However, between 15 and 30 per cent of the treated patients develop other skin tumours. By determining the mechanism by which these develop, we have been able to devise a strategy to prevent the second tumours without blocking the beneficial effects of the BRAF drugs. This may allow many more patients to benefit from these important drugs.”


Co-senior author Dr Antoni Ribas, a professor of hematology/oncology and a researcher with UCLA's Jonsson Comprehensive Cancer Center, said: “This is one of the very few times that we understand molecularly why a side effect to cancer treatment is happening. The side-effect in this case is caused by how the drug works in a different cellular setting. In one case it inhibits cancer growth, and in another it makes the malignant cells grow.”


Dr Julie Sharp, Cancer Research UK’s senior science information manager, said: “This research reveals a possible new approach to avoid the second cancers that affect some malignant melanoma patients taking BRAF inhibitors. The next stage will be to explore these results in more patients in clinical trials to see if this drug combination could treat the original cancer while preventing new cancers from forming.”




Media Contact: ICR Science Communications Manager Jane Bunce on 0207 153 5106 or after hours 077217 47900

Notes to editors:

The Institute of Cancer Research (ICR)

  • The ICR is Europe’s leading cancer research centre
  • The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise
  • The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe
  • The ICR has charitable status and relies on voluntary income
  • As a college of the University of London, the ICR also provides postgraduate higher education of international distinction
  • Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world
  • The ICR is home to the world’s leading academic cancer drug development team. Several important anti-cancer drugs used worldwide were synthesised at the ICR and it has discovered an average of two preclinical candidates each year over the past five years.

For more information, visit


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 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.

For further information about Cancer Research UK's work or to find out how to support the charity, please call 020 7121 6699 or visit


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