As well as being common and commonly lethal, prostate cancers are also pretty cunning, with an ability to resist hormone therapy that’s made treatments more difficult.
Now, insights gained from new research into how cancers evolve might help prevent prostate cancer from resisting therapy. The work has been published in Cell Reports.
Key research points
- Prostate cancers can evolve to resist hormone treatment
- microRNA miR-194 increased during hormone treatment
- miR-194 regulates many genes that promote cell change
- miR-194 can be blocked to prevent new cancer growth
A common hormone treatment for prostate cancer involves decreasing the activity of the androgen receptor, which is responsible for binding hormones like testosterone and transporting them deep into a cell.
Prostate cancers depend on these hormones, and so are starved when the receptors are blocked.
However, cancers can change very quickly to resist hormone therapy and grow into a new, aggressive subtype called neuroendocrine prostate cancer.
This occurs in up to 15% of patients. There’s currently no effective treatment for these types of potentially lethal prostate cancers.
Now, Australian researchers have found that this type of tumour adaptation is enhanced by a microRNA called miR-194, which can lead to the development of neuroendocrine prostate cancers in patients after therapy.
Blocking miR-194 may slow down, and even prevent, the growth of these new cancer cells.
Snapshot: prostate cancer
- There’s a 1 in 5 chance a man will be diagnosed with prostate cancer before age 85
- Prostate cancer was the second most lethal cancer – after lung cancer – to males in Australia in 2020
- 98% of men diagnosed with prostate cancer are over age 50
- Common symptoms of prostate cancer ares frequent urination, weak or interrupted flow of urine, pain or blood during urination
Led by Luke Selth of Flinders Health and Medical Research Institute, South Australia, the research team found that miR-194 greatly increased when androgen receptors were turned off, and these RNAs regulated a variety of genes that help boost cell plasticity – the ability for a cell to change.
“Increased cellular plasticity is increasingly recognised as a key feature by which prostate cancers become resistant to therapy and progress to a lethal stage,” says Selth.
They found that miR-194 regulated the process of genes creating proteins, and some of these proteins allowed the cancer cells to change and start showing features of neuroendocrine cancers, which resisted the hormone therapy.
However, they used an miR-194 inhibitor to block the microRNA and found that the new, aggressive cells stopped growing as rapidly.
“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,” says Selth.
The team used cancer cells from a deceased patient, so the technique is not yet ready for clinical application. But it’s an exciting step to overcoming a major roadblock for prostate cancer treatment.
“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 neuroendocrine prostate cancer or even prevent its emergence,” says Selth.
Dr Deborah Devis is a science journalist at The Royal Institution of Australia.
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