Discovery gives hope of detecting and preventing prostate cancer spread

Over 60% of Australian men with metastatic prostate cancer do not survive longer than 5 years past diagnosis, which means thousands of families each year lose loved ones to this aggressive form of cancer.

But there’s hope on the horizon thanks to the findings of a new study led by PhD student Harley Robinson and QIMR Berghofer Associate Professor Michelle Hill, who found lowering cholesterol could be the key to lifesaving diagnostics and possible prevention for metastatic patients, and made the discovery after identifying a change in function of a protein found in people with advanced prostate cancer.

Ms Robinson said in laboratory tests, researchers found lowering cholesterol can help control the release of hnRNPK protein from prostate cancer cells – released in small particles called exosomes – which prostate cancer cells send out to prepare other parts of the body for cancer spread.

“The exosomes act like a pre-planting conditioner that makes the environment in the new parts of the body receptive to the cancer cells when they eventually reach the site,” Ms Robinson said.

“Our lab work showed that reducing the cholesterol levels or boosting OMEGA-3 levels in the cells could stop the hnRNPK message from leaving the cancer cell and spreading its dangerous message.”

Associate Professor Hill, Head of QIMR Berghofer’s Precision and Systems Biomedicine Group and the senior study researcher, said these findings is a step towards a personalised treatment or prevention of prostate cancer spreading.

“This understanding of the role cholesterol plays in sending out these metastatic messages to other parts of the body, means we could potentially use statins (cholesterol inhibitors) or other cholesterol lowering drugs to prevent metastases,” Associate Professor Hill said.

“Conversely it might be possible to boost OMEGA-3 levels through supplements to protect against cancer spread.”

While prostate cancer that remains localised is highly curable, the survival rates for men with advanced prostate cancer are grim in comparison
and there is no specific test to detect cancer metastasis.

“Our pilot study of samples from eight prostate cancer patients revealed the release of hnRNPK outside the cell was 100 per cent accurate in predicting which patients would experience cancer spreading – despite treatment,” said Associate Professor Hill.

The team is now developing a prototype blood test to detect the level of released hnRNPK, which may one day be used to identify patients who should be given cholesterol lowering drugs to prevent metastases.

“We are hopeful a blood test using this biomarker would allow doctors to identify patients who should be given re-purposed cholesterol lowering drugs to prevent cancer spread, but also detect patients who are unlikely to have problems with metastases and therefore could safely avoid additional, morbid treatments.”

Dr John O’Hagan AM, a 100-year-old retired scientist, who has lived with prostate cancer for 40 years, is excited by these new findings. The founder of the Queensland Academy of Arts and Science, Dr O’Hagan is a staunch advocate for investment in medical research and initiated a donation from his local RSL Sub Branch to help fund the research.

Associate Professor Hill is grateful to Dr O’Hagan, the Stephens RSL Sub Branch and the Australian Research Council for providing funding for the study.

The researchers plan to soon evaluate a larger group of samples, which will be selected from a completed prostate cancer clinical trial.

“The findings are very exciting and we think this hnRNPK protein might play a role in metastases in other cancers as well, but it is early days and more research is needed to confirm the link,” Associate Professor Hill said.

The study involved collaborators from The University of Queensland, Griffith University, University of Western Australia and Ochsner Health Systems, New Orleans, USA.

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