Friday 25 June 2010
The way prostate cancer develops in men who have an altered ‘breast cancer gene’ is the same route by which breast cancer develops in women with the same mutation, reveals a study published in PLoS Genetics*.
Alterations in the gene BRCA2 have previously been linked to an increased risk of breast, ovarian and prostate cancers. But this is the first time scientists have been able to show the role the altered gene plays in tumour growth in the prostate.
Researchers, funded by Cancer Research UK, from the Section of Gene Function and Regulation and from the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR), have pinpointed early genetic changes that lead to cancer in mice lacking the BRCA2 gene in their prostate gland.
The researchers revealed that such alterations accumulate over time, increasing the risk of prostate cancer developing.
The discovery builds on research to show that a promising class of new drugs for BRCA2 linked breast cancers – known as PARP inhibitors** – may also be effective in men who have developed prostate cancer due to a BRCA2 alteration.
Lead author, Dr Amanda Swain, from the Section of Gene Function and Regulation at the ICR, said: “The discovery that BRCA2 alterations play the same role in the development of hereditary prostate cancer as they do in breast cancer is an important step.
“This sheds light on the relationship between the two conditions and could help highlight overlapping areas where similar treatments could be used to treat both.
“PARP inhibitors are a really promising class of drugs for women with faulty BRCA genes.
“One type of PARP inhibitor has already shown promise in a patient with advanced prostate cancer, and the early results are encouraging.”
The researchers examined cells taken from the prostate glands of mice lacking the BRCA2 gene, which is involved in DNA repair.
They found that these cells accumulated DNA damage faster than it could be repaired, leading to the build up of random DNA errors.
While not a direct cause of cancer, the researchers suspected that over time this could lead to key anti-tumour genes being damaged that would normally prevent cancer from developing.
To test if this was the case the researchers knocked out an additional gene known as p53, which is known to be faulty or missing in more than half of all cancers.
They found that the second faulty gene tipped the cells over the edge, causing widespread DNA damage and greatly increasing the likelihood of cancer developing.
Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “We’ve made great progress in developing drugs for hereditary breast cancer – particularly in targeting cancers caused by specific faulty genes through drugs like PARP inhibitors.
“It would be fantastic if these drugs could ‘multi-task’ and treat prostate cancer too.
“While we’ll need to see the results from more patients before we know if this drug could be used in men with this type of prostate cancer, this discovery shows that it’s an exciting possibility.”
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Notes to editor
* Francis et al. PLoS Genetics (2010), Brca2 and Trp53 Deficiency Cooperate in the Progression of Mouse Prostate Tumourigenesis, online at: http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000995
** A number of PARP inhibitors are currently being developed. One, known as Olaparib, was identified and developed at KuDOS Pharmaceuticals and subsequently at AstraZeneca, and is being tested at the ICR. Another, AGO14699, is being tested and developed by Cancer Research UK scientists based at Newcastle University.
About prostate cancer
Each year in the UK around 36,000* men are diagnosed with prostate cancer.
Prostate cancer often clusters in families and 5-10% of all prostate cancers may have a substantial inherited component. Searches for high-risk prostate cancer loci have identified the familial breast cancer gene BRCA2 as an important susceptibility factor. Carriers of germline mutations in BRCA2 have at least five times greater risk of prostate cancer and frequently develop a more aggressive form of the disease.
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, spending 90 pence in every pound of total income directly on research
- 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
For more information visit www.icr.ac.uk
About Breakthrough Breast Cancer
Breakthrough Breast Cancer is the UK’s leading charity committed to fighting breast cancer 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 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 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 thirty years
- Cancer Research UK supports research into all aspects of cancer through the work of more than 4,800 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