Discovery of ‘metastatic signature’ raises hopes of early identification of lethal disease
Deciding whether 'to treat or not to treat' localised prostate cancer is one of the biggest dilemmas for men and their doctors. Now new research from one of the Movember Centres of Excellence could help identify which cancers are likely to spread and which are harmless.
Researchers at the Belfast-Manchester Movember Centre of Excellence – funded by the Movember Foundation – have discovered a 'metastatic signature' in the genetic code of some prostate cancer cells, which could help identify which cancers are aggressive and which are harmless.
The fact that doctors can’t be 100 per cent certain about whether a prostate cancer requires treatment or not is one of the major problems facing men diagnosed with the disease today. Not treating a cancer that does in fact later progress could be fatal, while treating a cancer that would never cause any harm risks serious and potentially life-altering side effects.
But today's published research could represent the first step towards resolving the issue once and for all.
Taking a different approach to examining tumour samples
Previous tests that aimed to do a similar job have taken a patient outcome approach. This means they looked at biopsy samples from men whose cancers turned out to be aggressive and men whose cancers weren’t deemed harmful, and then looked for the differences between and similarities within each of these groups.
But in this new study, the researchers went about things slightly differently, looking at the underlying biology of the cancer itself without first knowing the outcome of the patient it was taken from.
They proposed that there might be a subgroup of primary prostate cancers that share genetic characteristics with metastatic disease (cancer that’s spread outside the prostate). Not only this, but the researchers suspected that these would be the particularly dangerous cancers that are likely to return and spread after a prostate surgery.
A cluster of 70 genes found expressed in aggressive samples
To test out this idea, they looked at the genes expressed by primary prostate cancers, primary prostate cancers with known metastases, metastatic lymph node samples, and prostate tissue that they knew had no cancer within it.
Sure enough, they found a cluster of 70 genes that were expressed the same in all the metastatic lymph node samples, all of the primary prostate cancers with known metastasis and some of the primary prostate cancer samples. Importantly, this gene expression pattern – or 'metastatic signature' – wasn’t shared by any of the normal tissue or the rest of the primary prostate cancer samples.
They then needed to confirm that these results really could predict which men were at risk of developing metastatic prostate cancer. So they tested their metastatic signature against publicly available sets of prostate biopsy samples, matched to clinical outcome. These tests confirmed that the metastatic signature could successfully identify primary prostate cancers that would eventually spread beyond the prostate.
Ending the biggest dilemma facing men at diagnosis
This is an important development, because the question 'to treat or not to treat' is still a big dilemma facing men diagnosed with prostate cancer and their doctors.
The researchers working on this project hope that this test could eventually help doctors identify which men wouldn't be safe to recommend for active surveillance, as well as instantly identifying men who are at risk of cancer recurrence after prostate surgery and so should be offered more radical treatment straight away.