- Largest ever study of advanced prostate cancer genomics reveals gene mutation identifying the most aggressive of prostate cancers
- Research could lead to test to improve treatment for these especially aggressive prostate cancers
- Study also found that a breast cancer drug plus immunotherapy might be a promising option for some men with prostate cancer
Scientists have identified a gene mutation in the tumours of men with prostate cancer that is linked to very poor survival - and which could be used to pick out patients for more intensive treatment.
Men with mutations in the retinoblastoma gene in their tumours were more than three times as likely to die and nearly seven times as likely to relapse on standard treatments as those without the gene.
The retinoblastoma gene, known as RB1, is so called because mutations in it cause a rare children's eye cancer of the same name and is known to play a central role in stopping healthy cells from dividing uncontrollably.
Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust believe testing men for the mutation could identify those with especially aggressive disease who need the most intensive available treatments. They are also studying new ways to treat patients with the high-risk gene.
The researchers, along with colleagues in the US and Europe, looked in detail at the DNA sequence, the activity of genes and how the tumours looked under the microscope in 444 tumours samples from 429 men with advanced prostate cancer.
Their study is published today (Monday) in the Proceedings of the National Academy of Sciences (PNAS), and was funded by the Prostate Cancer Foundation and Stand Up to Cancer.
The team wanted to identify which of the many genes linked to prostate cancer were the most important indicators of patient survival and response to the standard treatments abiraterone and enzalutamide.
Patients with mutations in the RB1 gene in their tumours were 3.3 times more likely to die and 6.6 times more likely to relapse during the course of the study than other men who also had standard treatment but did not have the mutation.
RB1 was the only gene found to have such an impact on survival, but mutations in two further genes - p53 and the androgen receptor gene - were associated with an increased risk of relapse on abiraterone or enzalutamide.
Mutations in DNA repair genes BRCA1, BRCA2 and ATM, and in PI3K genes were relatively common but had no impact on treatment with abiraterone or enzalutamide or on overall survival.
However, the research did identify clues for how some patients with prostate cancer could be treated more effectively using immunotherapy and a breast cancer treatment.
Men whose tumours had mutations in a gene linked to a good response to immunotherapy, CDK12, often also had mutations in the genes CDK4 and CCND1, which are the targets of a breast cancer drug called palbociclib.
That suggests that combining immunotherapy with palbociclib could be an effective treatment for this group of men.
Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation trust, said:
"Our study really got under the bonnet of prostate cancer to understand the 'engine' driving tumour growth and explore how a wide range of genes affect the disease and its response to treatment. We identified one particular genetic mutation that seems to indicate that tumours are going to be very aggressive, and that the affected men need the most intensive treatment we have available.
"Our research could also open up various new approaches to prostate cancer treatment, and offers the intriguing suggestion that some patients could benefit from immunotherapy alongside an existing breast cancer drug. That's a great example of how genetic research can find the common links between cancers, and ensure research into one cancer type can also benefit patients with other tumours."
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:
"There are a large number of genetic mutations present in a tumour, and working out their relative importance is crucial to deliver the best precision medicine to cancer patients.
"This exciting study has identified which features of advanced prostate tumours are the most important for treatment and survival - and has picked out one gene mutation in particular which has an especially serious adverse impact on how long patients live.
"The crucial thing now is that we make use of this information, by developing a test to identify affected men and to make sure they receive the best treatments we have available today, while also focusing our efforts on improving options for the future."
###
For more information please contact Claire Hastings in the ICR press office on 020 7153 5380 or claire.hastings@icr.ac.uk. For enquiries out of hours, please call 07595 963 613.
Notes to editors
The Institute of Cancer Research, London, is one of the world's most influential cancer research organisations.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives.
Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four centres for cancer research and treatment globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease.
Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
A college of the University of London, the ICR is the UK's top-ranked academic institution for research quality, and provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk
ABOUT THE PROSTATE CANCER FOUNDATION
The Prostate Cancer Foundation (PCF) is the world's leading philanthropic organization funding and accelerating prostate cancer research. Founded in 1993, PCF has raised more than $788 million and provided funding to more than 2,000 research programs at nearly 200 cancer centers and universities. The PCF global research enterprise now extends to 19 countries. PCF advocates for greater awareness of prostate cancer and more efficient investment of governmental research funds for transformational cancer research. Its efforts have helped produce a 20-fold increase in government funding for prostate cancer. For more information, visit http://www.pcf.org<http://www.pcf.org>.
Journal
Proceedings of the National Academy of Sciences