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Gene mutations can predict prostate cancer drug resistance

09 November 2015

By Kirsty Oswald

Appeared in BioNews 827

Researchers have identified the genetic mutations that drive resistance to the hormone therapy abiraterone in patients with advanced prostate cancer.

As these mutations were detected prior to treatment, they say the findings could be used to identify men who would be more suited to alternative therapies, such as chemotherapy or radiotherapy.

The researchers used blood samples taken from 97 patients with advanced prostate cancer to detect circulating tumour DNA (ctDNA). These patients all had a form of prostate cancer known as 'castration resistant', which has stopped responding to first-line treatment with androgen-deprivation therapy. Using the blood test meant that the researchers were able to detect DNA from metastases, which are challenging to obtain traditional biopses from.

They found that men who had particular point mutations or additional copies of the androgen receptor (AR) gene had poorer responses to abiraterone than men without these variants. They were 4.9 and 7.8 times less likely to have a decline of at least 50 or 90 percent, respectively, in prostate-specific antigen – a key marker of disease progression. These patients also had significantly poorer progression-free and overall survival.

Overall, 45 percent of the men tested had one of these mutations before treatment, and 13 percent also developed a point mutation during treatment.

Additionally, patients with higher levels of ctDNA detected tended to have poorer outcomes than patients with lower ctDNA concentrations.

The researchers, who report their findings in Science Translational Medicine, say that they are now planning a clinical trial to explore whether men who test positive for AR mutations fare better on chemotherapy than abiraterone or other drugs.

'Critically, we believe that this sort of technology would be relatively straightforward to implement in NHS hospitals, making it accessible to a large number of patients,' said lead researcher Dr Gerhardt Attard from the Institute of Cancer Research.

'Additionally, looking at tumour DNA in the blood of patients could potentially give us an overall picture of why the cancer is progressing all over the body, unlike a biopsy that only tells us about the area sampled,' he added.

Last year, NICE, National Institute for Health and Care Excellence, rejected abiraterone for prostate cancer, outside of end-of-life care, due to concerns over data presented by the manufacturer Janssen and over costs. Therefore, campaigners hope that the test, by identifying patients most likely to respond, could help increase the availability of the drug.

'We know that a one-size-fits-all approach to treating prostate cancer doesn't work,' said Dr Iain Frame, Director of Research at Prostate Cancer UK.

'When the clock is ticking for a man with advanced prostate cancer, finding out early that his treatment needs changing can not only save precious time, but can also help avoid unpleasant side effects from a treatment that no longer works for him.'

BBC News | 05 November 2015
NHS Choices | 05 November 2015
Institute of Cancer Research (press release) | 04 November 2015
GenomeWeb | 04 November 2015
Science Translational Medicine | 04 November 2015


26 June 2017 - by Charlotte Spicer 
A new three-in-one blood test could progress personalised treatment for patients with prostate cancer...
16 January 2017 - by Annabel Slater 
Canadian scientists have identified a genetic fingerprint that indicates which prostate cancer tumours may develop into a more aggressive form of the disease after treatment...
19 December 2016 - by Isobel Steer 
A study has cast doubts on the reliability of 'liquid biopsies' – blood tests that detect tumour mutations and are increasingly used to guide treatment...
14 March 2016 - by Dr Lucy Freem 
Scientists have developed a blood test that captures tumour DNA from stray cancer cells circulating in the blood and allows them to monitor genetic changes in skin cancer...
15 February 2016 - by Helen Robertson 
A blood test to diagnose common types of cancer is in development after researchers found that five forms of the disease share a telltale chemical signature...

02 November 2015 - by Dr Jane Currie 
A drug that targets genetic mutations in ovarian cancer has been found to work in men with prostate cancer with similar mutations, according to a new study...
03 August 2015 - by Kirsty Oswald 
Researchers have found that prostate cancer can be divided into five subgroups with distinct genetic fingerprints...
26 May 2015 - by Dr Julia Hill 
Scientists have announced a comprehensive genetic map of prostate cancer, which they say could lead to new treatments for the advanced stage of the disease...
22 September 2014 - by James Brooks 
A study where the tumour DNA of 16 prostate cancer patients was frequently checked suggests that, in some patients, commonly used anti-cancer drugs may actually boost tumour growth after a while...
14 April 2014 - by Simon Hazelwood-Smith 
A genetic test has been developed to predict the likelihood of prostate cancer returning after treatment. The test looks for 'genetic signatures' often found in recurring cancers...

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