Canadian scientists say they’ve discovered the genetic fingerprint behind why some men with curable prostate cancer end up developing an aggressive form of the disease that spreads and ultimately kills them.
The doctors out of Princess Margaret Cancer Centre say their findings published Monday could pave the way to carving out personalized, targeted therapies from the moment of diagnosis.
Turns out the BRCA 2 gene, which gained notoriety after Angelina Jolie shed light on how its mutation increases risk of breast and ovarian cancer, also increases risk of prostate cancer in men, and makes the disease much more lethal.
“We knew that patients who had a mutation in the BRCA 2 gene had increased death rates from prostate cancer but no one had studied them because they’re so rare,” study co-author, Dr. Robert Bristow, told Global News.
He’s a clinician scientist at Princess Margaret and teaches radiation oncology at the University of Toronto.
“BRCA 2’s purpose is to repair DNA damage in cells that occur everywhere. If it’s abnormal, it doesn’t repair damage that accumulates leading to mutations in chromosomal changes,” he warned.
For a pair of studies, Bristow worked with colleagues close by from the Ontario Institute for Cancer Research and Laval University in Quebec City, along with scientists in Melbourne, Australia.
For starters, Bristow and his team looked at the tumours of 500 Canadian men with prostate cancer. Their cancers were isolated and non-inherited. They compared gene sequencing and the cancer’s progression next to 15 men with prostate cancer and the BRCA 2 gene.
“Because the differences were so profound relative to the 500 patients, we could make a conclusion that there are specific changes that occur early in the BRCA 2 tumours that make them more aggressive,” Bristow explained.
The men with the BRCA 2 mutation had tumours that are “already pre-set” to be aggressive, which may explain why these cancer cases are resistant to certain treatments, like hormone therapy.
The BRCA 2 gene mutation affects fewer than two per cent of men. But those who carry the BRCA 2 gene mutation have a five to eightfold increased risk of prostate cancer compared to their counterparts without the mutation.
In men who end up with prostate cancer, only 50 per cent survive if they have the BRCA 2 gene compared to survival rates of up to 80 per cent in the general population. The cancer is generally slow to progress and not life-threatening.
Bristow said men could undergo genetic testing to screen for the mutation. It’s as simple as a DNA test of white blood cells in patients. If they carry the mutation, treatment would differ in that doctors would monitor more closely and carry out aggressive treatment options at the onset, Bristow said.
Surgery and radiation, for example, would consider the entire body to “mop up” cancer cells in case they spread. They could even prescribe specific molecular targeted drugs that prey on the BRCA 2 gene mutation.
“We’d take advantage of the defect of the BRCA 2 patient and choose treatments that are more potent in this group,” he said.
The next steps are to build clinical trials for the specific subset of prostate cancer patients. Keep in mind, the BRCA 2 gene mutation is incredibly rare – about 200 prostate cancer patients carry the mutation in Canada, Bristow estimates.
It could take about five years for more findings to come out of Bristow’s research as clinical trials are pulled together.
But Bristow said the latest research pushes personalized cancer care forward. The plan is to test 500 more men over the next two to three years.
“We will soon be able to identify in the clinic the exact state of a man’s cancer and react on a patient-to-patient basis to cure more men worldwide,” Bristow said.
His findings were published Monday in the journal Nature.
The research was supported by Movember funds through Prostate Cancer Canada, the Ontario Institute for Cancer Research, the Canadian Institutes for Health Research, the Canadian Cancer Society, and The Princess Margaret Cancer Foundation.
Read the full findings here.