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Turning of pieces of genetic ‘dark matter’ could fight hard-to-treat prostate cancers

Scientists have discovered a new piece of genetic code involved in prostate cancer – and tampering it could offer hope to patients with the toughest types of the disease. 

Prostate cancer is the second most common cancer in men, and is typically treated by blocking male hormones, androgen, high levels of which trigger tumor growth. 

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But men with the most aggressive forms of the disease often become resistant to treatments that target the hormone and it’s receptors directly. 

Now, scientists at the University of Michigan have found a piece of the genome’s ‘dark matter’ that sends signals for the dangerous hormone to be released. 

Experimenting with mice, they found that by turning off the gene, they could cut the whole network that leads to androgen release so cancer cells start to die off. 

Many men become resistant to prostate cancer treatments that cut the hormones that feed the disease, but doctors have found a new treatment target that could work for stubborn cancers 

One in every 10 men in the world will get prostate cancer some time in their lives, meaning that every year about 165,000 new cases are diagnosed.  

The same hormones that play a key role in the development and function of the prostate – a male reproductive gland involved in semen production – and other parts of the reproductive system can cause cancer. 

Called androgens, these hormones include testosterone and dihydrotestosterone (DHT), both of which help men to develop the characteristics we associate with maleness. 

But androgenes fuel receptors in the prostate that can turn on the expression of parts of the genome that code for the growth of prostate cells in adults, and these cancerous cells can multiply out of control. 

Many prostate cancers need a lot of androgens to feed off of and grow in their early stages, so doctors often starve them out using treatments to block androgens to slow down the growth of the tumors. 

Doing this – by surgically removing the testicles, through hormonal drug therapies, or a combination of  the two – is called castration. 

However, most patients eventually become resistant to this treatment and androgen production ramps right back up, so it is certainly not a cure. 

In the new study, the Michigan doctors discovered a piece of genetic material that could offer a new way to interfere with the androgen cycle and slow cancer growth. 

Our genome is composed of DNA – the raw genetic information – and RNA, the biochemical messengers that carry out DNA’s instructions. 

But a large portion of the genetic code remains mostly unknown, earning it the nickname of ‘dark matter.’ 

In 2015, the Michigan researchers, led by Dr Arul Chinnaiyan discovered  thousands of messenger components in this ‘dark matter,’ called IncRNAs. 

During the course of their new study, they found that one of these – ARLNC1 – is linked to the development of prostate cancers. 

Signals from androgen receptors, they discovered, turned ARLNC1 on. Essentially, the piece of genetic information, the hormone and its receptors form a feedback loop that stimulates cancer growth. 

The link was further solidified when Dr Chinnaiyan and his team blocked ARLNC1 in mice, and found that cancer cells started dying off, and developing tumors stopped growing. 

When they turned on more ARLNC1, the reproduction of cancer cells ramped up, and knocking the RNA back down again was immediately followed by tumor shrinkage. 

‘The androgen receptor is an important target in prostate cancer. Understanding that target is important. 

‘This study identifies a feedback loop that we could potentially disrupt as an alternative to blocking the androgen receptor directly,’ said Dr Chinnaiyan.

In the future, ‘we’re envisioning a potential therapy against ARLNC1 in combination with therapy to block the androgen receptor – which would hit the target and also this positive feedback loop,’ he added. 


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