Newly discovered genetic fingerprint for prostate cancer promises to personalize treatment

University of Toronto scientists have found genetic abnormalities that may predict aggressive forms of prostate cancer.

Scientists at the University of Toronto have discovered a set of genetic mutations that they believe will help oncologists predict when men with localized prostate cancer are most at risk for seeing their disease spread after treatment. The research, published in the journal Nature, describes a genetic “fingerprint” for the 30% of men whose cancer is thought to be curable because it’s localized to the prostate, but who go on to suffer aggressive metastasis.

The researchers developed the fingerprint by investigating the tumors from 500 men diagnosed with prostate cancer, according to a press release from the university. Using DNA sequencing, they studied the primary genetic differences between the tumors from men who responded well to surgery or radiation and those from patients who didn’t.

They found that almost 50% of men with metastatic disease have mutations in four specific genes, while more than 60% have mutations for which there are targeted treatments available, according to the paper. They also discovered that about 20% of men with aggressive prostate cancer have abnormalities in the genes BRCA1, BRCA2 and ATM. That could make them good candidates for treatment with PARP inhibitors, which promote tumor cell death in cancers that harbor those mutations.

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“This information gives us new precision about the treatment response of men with prostate cancer and important clues as to how to better treat one set of men versus the other to improve cure rates overall," Robert Bristow, a clinician and scientist at the University of Toronto’s Princess Margaret Cancer Centre, said in the release.

Prostate cancer researchers are pursuing myriad strategies for preventing the disease from spreading. Last year, scientists at MD Anderson described their discovery of a protein called ZMYND8, which they believe influences gene expression in ways that may prevent metastasis.

The notion of using PARP inhibitors to treat prostate cancer is likely to generate interest in the oncology community as well. PARP inhibition is a new and fast-growing class of cancer treatment being examined for its potential in several tumor types. For example, in October, scientists at the University of Maryland showed that combining PARP inhibition with an epigenetic modifier could slow cancer growth in acute myeloid leukemia. The PARP inhibitor Lynparza (olaparib) has been approved for BRCA-mutated ovarian cancer and is being studied in breast cancer, as well.

Bristow and his colleagues at the University of Toronto hope to develop a diagnostic test based on their discovery of a genetic fingerprint for aggressive prostate cancer. But first they need to test their findings in another trial, which will include 500 men and take two to three years, he said in the release. “We will soon be able to identify in the clinic the exact genetic state of a man's cancer,” he said, “and react on a patient-to-patient basis to cure more men worldwide."

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