How prostate cancers become drug resistant discovered

London: Scientists have discovered that some forms of prostate cancer evolve at a super-fast rate to become "hypermutated" and resistant to treatment, a finding they say could lead to new targeted drugs for the life-threatening disease.

A team of researchers in the US made the discovery after mapping the genetic codes of 23 aggressive and drug-resistant forms of the disease.

They identified three tumour types that had 10 times more mutations than other advanced prostate cancers.

The findings, they said, could provide clues to why some prostate cancers are so lethal and eventually lead to screening tests for men at high risk, the Daily Mail reported.

Understanding the genetic links to prostate cancer could also aid the development of new targeted drugs and aid doctors in making decisions about prescribing treatment, they said.
Study co-author Dr Peter Nelson, from the Fred Hutchinson Cancer Research Centre in Seattle, said: "We don`t know the cause of these hypermutated tumours, but the frequency of the mutations suggests these tumours might evolve very rapidly to develop resistance to therapies."

The cancers studied originated from tumour samples taken from patients and held at the University of Washington. They were grown in immunodeficient mice before having their DNA analysed. The cancers included those that had spread around the body and some which had not but were aggressive.

The scientists, who detailed their finding in the journalProceedings of the National Academy of Sciences, focused on the exome, the one per cent of the genetic code that contains the "software" for making proteins. It is this region that harbours the majority of disease-causing mutations.

The researchers identified a number of genes containing mutations including one known as p53 -- which is a well-known tumour-suppressing protein.

Another gene, glypican-6, also harboured mutations while recurrent variants were also found in several genes whose mechanisms in prostate cancer development are not yet well understood.

"By sequencing the exomes of 23 tumours representing a spectrum of aggressive advanced prostate cancers, we identified a large number of previously unrecognised
gene-coding variants with the potential to influence tumour behaviour," the researchers wrote.

Prostate cancer is the second most common cancer in men worldwide. Around 910 000 cases of prostate cancer were recorded in 2008, accounting for around 14 per cent of all new cancer cases in men. It is predicted that the number of cases will almost double (1.7 million) by 2030.


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