Skin Cancer Drug Development Boosted with £3m Grant
Wednesday 16 November 2011
The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust are to progress into patient trials an experimental drug to combat the most deadly form of skin cancer.
The BRAF-inhibitor has the potential to treat more sub-types of malignant melanoma than any other targeted treatments for this cancer. Scientists also believe that it will not cause the serious side-effect of squamous cell carcinoma that has been linked to an existing treatment.
The project has attracted a £3million commitment from the Wellcome Trust, who will work with the ICR and The Royal Marsden through their Strategic Translation Award programme to further refine the candidate compounds and take the most promising into the clinic.
Principal Investigator Professor Caroline Springer from the ICR says: “Our compounds are showing a lot of promise in the laboratory and it’s very exciting that soon one will be available to patients through a clinical trial. It’s very rare for drug development to be advanced to the clinical trial stage without the involvement of a pharmaceutical company, so the Wellcome Trust’s commitment is a testament to the strength of our work so far.
“Compared to the existing drug, our compounds have the potential to treat more tumour types – potentially three-quarters of all malignant melanomas - and we also believe we have found a way to prevent a significant side-effect. This illustrates how basic scientific research into understanding the molecular and genetic causes of cancer is so important in making sure patients receive the best possible care.”
Both the first targeted treatment for malignant melanoma, Roche-produced vemurafenib (Zelboraf), and the new compounds are based on research at the ICR showing that the mutated BRAF gene is driving cancer development in around 50 per cent of malignant melanomas. In addition to inhibiting BRAF, the new compounds are also expected to block the action of another mutated gene, called RAS, which drives a further 25 per cent of malignant melanomas. Blocking these faulty genes should cause cancer cells to die and tumours to shrink.
One recognised side-effect of vemurafenib is that it can induce another type of skin cancer, called squamous cell carcinoma, in some patients who receive the drug. Earlier studies at the ICR showed that these carcinomas may be triggered when vemurafenib blocks the normal BRAF in cells in which RAS is faulty. This is thought to lead to a protein related to BRAF called CRAF becoming activated, which drives these carcinomas.
Scientists at the ICR have already developed a series of compounds that block both BRAF and CRAF and shortlisted the two most promising versions.
The new funding will enable the team in the ICR’s Cancer Research UK Cancer Therapeutics Unit to select the best drug candidate for initial safety testing and determine an appropriate dose to give to patients. Clinicians in The Royal Marsden Hospital’s Melanoma Unit will then lead early clinical trials. The team will also examine the different types of melanoma for which the drug is effective, including whether it can benefit patients who have relapsed after taking vemurafenib.
Dr James Larkin from The Royal Marsden said: “We are delighted by this partnership between The Royal Marsden, the ICR and the Wellcome Trust and are thrilled by the commitment from the Wellcome Trust to our research. We know that BRAF inhibitors such as vemurafenib benefit a large number of melanoma patients with BRAF mutations but most patients become resistant to treatment. Therefore there is a need to develop more effective drugs and also to target melanomas which do not have BRAF mutations.”
The incidence of malignant melanoma is increasing in the UK, with around 10,000 people diagnosed and 2,300 deaths a year. The disease is difficult to treat once it has spread to other organs.
BRAF-targeting drugs may also be important in other tumour types, as mutations in this gene are common in thyroid cancer (45 per cent of cases), ovarian cancer (10 per cent), and colorectal cancers (13 per cent).
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Media Contact: ICR Science Communications Manager Jane Bunce on 0207 153 5106 or after hours 077217 47900
Notes to editors:
The Wellcome Trust, Cancer Research UK, The Institute of Cancer Research and Astex Pharmaceuticals all contributed funding to the BRAF drug discovery and development programme.
Professor Richard Marais and Professor David Barford from the ICR originally solved the crystal structure of the drug, creating a 3D model of the way the drug interacts with the mutated BRAF protein. A team led by Professor Caroline Springer and Professor Marais at the ICR discovered four novel series of compounds that are potent BRAF inhibitors. The compounds were shown to be orally active in a number of xenograft models and three lead pre-clinical candidates were selected.
Professor Springer from the ICR is principal investigator on the grant and will lead on pre-clinical assessment. The other grant awardees are lead clinician Dr James Larkin from The Royal Marsden, Professor Martin Gore from The Royal Marsden and Professor Richard Marais from the ICR.
A commercial partner is being sought to assist the further development of the drug.
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 www.icr.ac.uk
The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education.
Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe treating over 44,000 patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies. The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex.
Since 2004, the hospital’s charity, The Royal Marsden Cancer Charity, has helped raise over £50 million to build theatres, diagnostic centres, and drug development units. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.
For more information, visit www.royalmarsden.nhs.uk
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.
www.wellcome.ac.uk
