Thursday 27 August 2009
Cancer Research UK-funded scientists have shown that an early chemotherapy drug invented in the 1940s has the potential to work against a genetic fault called HNPCC* which is linked to bowel and other cancers. The results are published in EMBO Molecular Medicine** today, (Thursday).
HNPCC is a hereditary condition involved in around five per cent of all bowel cancer cases. As well as bowel cancer, it puts people at increased risk of developing stomach, womb, ovarian, kidney and other cancers. Almost 40 per cent of people with HNPCC have a faulty MSH2 gene.
Scientists at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR) in London sought to improve treatments for people with cancer caused by HNPCC by finding drugs which selectively kill cells containing the damaged MSH2 gene. In this study, the scientists tested a range of drugs on cells with the faulty MSH2 gene. They found that a drug called methotrexate*** worked particularly well in destroying these cells.
This study suggests that methotrexate could help to treat people whose cancer is driven by the MSH2 genetic fault, potentially opening the door to a more targeted treatment option. A new clinical trial has begun at The Royal Marsden NHS Foundation Trust to see how well methotrexate treats patents with advanced bowel cancer following this study****.
Methotrexate is similar to a normal molecule called folinic acid, which is required for copying DNA. The drug prevents cells from making and repairing DNA - a process needed for cancer growth. It was one of the first chemotherapy drugs to be invented in the 1940s and is still used to treat a number of cancers today. But until now, it has not commonly been used to treat people with HNPCC.
Professor Alan Ashworth, who led this Cancer Research UK-funded study at the ICR, said: "The MSH2 gene plays a vital role in repairing DNA damage but if it is faulty, mistakes accumulate in cells and increase the risk of cancer developing.
"What's exciting about methotrexate is that it selectively destroys the cells lacking the MSH2 function. This indicates that it may make an excellent treatment for patients with the genetic alteration. With our colleagues at The Royal Marsden Hospital, we have set up clinical trials to test this."
Dr Lesley Walker, director of cancer information at Cancer Research UK said: "In the past, many treatments were developed which indiscriminately kill dividing cells. With improved scientific understanding, we are starting to be able to offer targeted therapies that are selective for the genetic faults in cancer. It's really fascinating that our scientists have discovered that an old-fashioned drug of this type shows new promise for this very specific group of patients.
"This is the first time scientists have identified a drug that targets cells lacking functional MSH2 genes. The chemotherapy drug methotrexate has already shown benefit for patients with breast, bladder and bone cancer as well as some types of leukaemia. We now need to find out if it is effective in patients with MSH2 gene defects."
- ENDS -
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Notes to editors:
*Hereditary non-polyposis colorectal cancer (HNPCC) is a hereditary condition which gives people a predisposition to developing some forms of cancer. It is also known as Lynch syndrome.
** Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the DNA mismatch repair gene MSH2. EMBO Molecular Medicine. Martin et al. August 2009.
***You can find our more about the drug methotrexate on Cancer Research UK's patient information website CancerHelp UK www.cancerhelp.org.uk
**** You can find out more about this trial on Cancer Research UK's clinical trials database CancerHelp UK http://www.cancerhelp.org.uk/trials/trials/trial.asp?=&trialno=20942
About The Institute of Cancer Research
The Institute of Cancer Research (ICR) is Europe's leading cancer research centre with expert scientists working on cutting-edge research. In 2009, the ICR marks its 100 years of groundbreaking research into cancer prevention, diagnosis and treatment. The ICR is home to the world's leading academic drug development team, which has developed many drugs now used as standard cancer treatments. It continues to be at the forefront of drug development, discovering an average of two preclinical candidates each year over the past five years. In December 2008, the ICR was ranked as the UK's leading academic research centre by the Times
Higher Education's Table of Excellence, based on the results of the Higher Education Funding Council's Research Assessment Exercise. The ICR is a charity that relies on voluntary income. For more information visit www.icr.ac.uk.
About Breakthrough Breast Cancer
Breakthrough Breast Cancer is a pioneering charity changing lives through research, campaigning and education. In 1999 Breakthrough established the UK's first dedicated breast cancer research centre. The Breakthrough Toby Robins Breast Cancer Research Centre is housed in the Mary-Jean Mitchell Green building at The Institute of Cancer Research in association with the Royal Marsden Hospital.
Under the directorship of Professor Alan Ashworth FRS, the Breakthrough Research Centre now has 120 world-class scientists and clinicians tackling breast cancer from all angles - from understanding the normal growth and development of the breast, how breast cancer arises and how the cancer spreads, to treatment and ultimately disease prevention. Scientists at the Breakthrough Research Centre have a range of expertise and approaches and together they are working towards a common goal: a future free from the fear of breast cancer. For more information, visit www.breakthrough.org.uk.
About the Journal EMBO Molecular Medicine
EMBO Molecular Medicine is a peer-reviewed journal, dedicated to the publication of original, cutting-edge research in the field of Molecular Medicine. Molecular Medicine is a rapidly-growing area of research at the interface between clinical research and basic biology. The Journal publishes research articles and reviews relevant to all fields of clinical medicine and their related research areas in basic biology. The European Molecular Biology Organization (EMBO) promotes excellence in molecular life sciences in Europe by recognising and fostering talented scientists, empowering them to advance the field of molecular biology. For more information please visit www.embomolmed.org.
About EMBO
The European Molecular Biology Organization (EMBO) promotes excellence in molecular life sciences by recognizing and fostering talented scientists, empowering them to advance the life sciences to understand how life works and share knowledge to help address the challenges of a changing world. For details about EMBO and its activities please visit www.embo.org.
About Cancer Research UK
- Cancer Research UK is the world's leading charity dedicated to beating cancer through research.
- The charity's groundbreaking work into the prevention, diagnosis and treatment of cancer has saved 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 thirty years.
- Cancer Research UK supports research into all aspects of cancer through the work of more than 4,500 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 www.cancerresearchuk.org.