New hope in fight against therapy-resistant prostate cancer
Cellular ‘switch’ identified that can trigger an aggressive sub-type of the disease following treatment.
Prostate cancer is one of the most common cancers in the UK, with around 48,500 men being diagnosed each year.
Now, Australian researchers have identified a mechanism in which prostate cancer cells can 'switch' character and become resistant to therapy, giving hope for new treatments.
These findings, published in Cell Reports, are an important development in unravelling how an aggressive subtype of prostate cancer, neuroendocrine prostate cancer (NEPC), develops after therapy.
The prostate is a small, walnut-sized gland at the base of the bladder that surrounds part of the urethra - the tube that carries urine from the bladder to the penis. Cancerous cells can develop in the prostrate leading to the growth of tumours, with older men being particularly at risk.
It is well established that some tumours show increased cellular 'plasticity' in response to new or stressful conditions, such as cancer therapy, says lead researcher Associate Professor Luke Selth, from the Flinders Health and Medical Research Institute.
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This plasticity allows the cancer cells to adapt and continue to grow by evolving into different cell types that no longer respond to the therapy.
“Increased cellular plasticity is increasingly recognised as a key feature by which prostate cancers become resistant to therapy and progress to a lethal stage,” he said.
“Our new study reveals that a particular molecule, the microRNA 'miR-194', can enhance this plasticity in prostate cancer, leading to the emergence of NEPC.
“By targeting miR-194, we were able to slow down and inhibit the growth of prostate cancer models with neuroendocrine features.”
Associate Professor Selth says while this study is a long way from clinical application, it nevertheless provides us with important new insights into how prostate cancers 'evolve' in response to therapy.
An estimated 15 per cent of men may develop this aggressive subtype of prostate cancer after hormonal treatment and there are currently no effective treatments.
“By revealing another regulator of prostate cancer cell plasticity that can promote evolution of tumours, our study highlights why prostate cancer is so difficult to cure,” Associate Professor Selth said.
“While this reality is sobering, we hope that our study and lots of other research going on around the world will eventually lead to smarter, more targeted ways to treat NEPC or even prevent its emergence.”
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Reader Q&A: How does radiation kill cancer if it causes cancer?
Asked by: Odysseus Ray Lopez, US
It’s rather like the way guns can be used to commit crime, or stop it. Radiation causes cancer because its high-energy photons can cause breaks in the DNA strands in your cells. Cells can repair this damage up to a point, but sometimes the repair isn’t perfect and leaves some genes defective.
If the break affects one of the many tumour-suppressing genes in your DNA, that cell can become cancerous. But cancer cells are also more vulnerable to radiation than ordinary cells. Part of what makes them cancer cells is their ability to divide rapidly and this normally means that some of the DNA ‘spellcheck’ mechanisms are turned off.
So when a cancer cell suffers a break in a DNA strand, it’s less likely to repair it correctly. Depending where the break occurs, it might either kill the cell outright, or make it reproduce more slowly.
Radiation therapy uses a focused beam that is aimed at just the part of the body with the tumour, and the dose is carefully calculated to cause the minimum collateral damage to healthy cells. Even so, radiation therapy does very slightly increase your chances of developing a second cancer.
Jason is the commissioning editor for BBC Science Focus. He holds an MSc in physics and was named Section Editor of the Year by the British Society of Magazine Editors in 2019. He has been reporting on science and technology for more than a decade. During this time, he's walked the tunnels of the Large Hadron Collider, watched Stephen Hawking deliver his Reith Lecture on Black Holes and reported on everything from simulation universes to dancing cockatoos. He looks after the magazine’s and website’s news sections and makes regular appearances on the Instant Genius Podcast.