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 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 showing 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.”
For media enquiries please call the Cancer Research UK press office on 020 7061 8309 or the out of hours’ duty press officer on 07050 264059.
Francis J.C., et al. Brca2 and Trp53 Deficiency Cooperate in the Progression of Mouse Prostate Tumourigenesis (2010), PLoS Genetics, DOI: 10.1371.
Notes to editors
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.