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Scientists create 'genetic map' of prostate cancer

26 May 2015

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.

The research found that nearly 90 percent of men with advanced prostate cancer have genetic mutations which could be targeted for treatment with existing drugs or drugs in clinical trials.

Professor Johann de Bono of the Institute of Cancer Research, London, and a lead author on the study told the BBC that the findings were a 'game-changer'. 'In the past, we used to treat lethal prostate cancer as a single illness but this shows that it is a group of diseases, each driven by their own set of mutations,' he said.

Researchers analysed the genetic code of tumour samples from 150 patients in whom the cancer had spread to the bones, soft tissue, lymph nodes and liver, to search for common mutations in the tumours.

The study, published in Cell, found that two out of three men studied had mutations in the receptor for the androgen hormone - the target of standard hormone therapy to which patients frequently develop resistance.

The findings could also open new directions for research into alternative hormone therapies. The researchers found that one in five patients had mutations in the genes BRCA1 and BRCA2. These genes are associated with an increased risk of breast and ovarian cancer and there are already drugs in development which target mutations in them.

Research findings presented in April, have already shown that a drug from a class that targets these mutations - called PARP inhibitors - is effective in patients with advanced prostate cancer.

Professor de Bono and colleagues also analysed blood samples from the patients to examine the non-tumour genome and found that eight percent were born with germline mutations which predisposed them to prostate cancer, a finding which could help develop predictive tests for the disease and lead to early diagnosis.

Over 40,000 men in the UK are diagnosed with prostate cancer each year, and more than 10,000 die after developing metastatic (advanced) prostate cancer. Nearly all men with metastatic prostate cancer develop resistance to hormone therapy, the standard treatment for the disease, after which there are limited alternatives.

These are the first findings to link this resistance to specific DNA mutations in fresh biopsies from living patients. The researchers say that using genetic testing could enable doctors to tailor patient care to their specific mutations, and develop a personalised method of treatment. For the next phase of their research, they plan to sequence the tumour DNA of at least 500 men with advanced prostate cancer and see how personalised treatments alter the disease course.

Dr Iain Frame, director of research at Prostate Cancer UK, told The Telegraph, 'Many of the genetic changes they have identified could potentially be targeted by existing drugs. The next step is to confirm whether those drugs would have the same impact if used to target those mutations when found in prostate cancer.'

SOURCES & REFERENCES
Integrative Clinical Genomics of Advanced Prostate Cancer
Cell |  21 May 2015
Prostate cancer breakthrough as scientists crack genetic code behind nine in 10 tumours
The Telegraph |  21 May 2015
Prostate cancer gene map points way to targeted drugs
BBC News |  21 May 2015
Prostate cancer 'Rosetta stone' paves way to targeted drugs
The Guardian |  22 May 2015
Scientists unveil prostate cancer's 'Rosetta Stone'
Institute of Cancer Research (press release) |  21 May 2015
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