A gene signature can predict whether localized prostate cancer will spread

The prostate is a tiny gland in the male reproductive system that is located in the pelvic. It’s roughly the size of a walnut and sits between the penis and the bladder, encircling the urethra. When cells in the prostate gland begin to grow out of control, prostate cancer develops.

It may not cause any symptoms at first. Symptoms in the later stages include pain or trouble urinating, blood in the urine, and pelvic or back pain. Adenocarcinomas, which arise from gland cells, account for nearly all prostate malignancies.

Researchers have discovered a genetic signature in locally advanced prostate cancer that can predict whether cancer will spread, or metastasis, early in the illness’s course and whether it will respond to anti-androgen therapy, a standard treatment for advanced disease. The novel gene signature could also be used to assess therapy responses and create new medicines to prevent or treat advanced prostate cancer.

Prostate cancers can grow and spread quickly in some cases, although most do not. In reality, postmortem examinations have revealed that many older men (and even some younger men) who died of various causes also had prostate cancer that they had never experienced during their lifetimes. In many situations, neither they nor their doctors were aware that they were suffering from it.

“If we could know in advance which patients will develop metastases, we could start treatments earlier and treat cancer more aggressively,” says the study’s senior author, Cory Abate-Shen, Ph.D., chair of the Department of Molecular Pharmacology and Therapeutics, the Michael and Stella Chernow Professor of Urologic Sciences (in Urology), and professor of pathology & cell biology (in the Herbert Irving Comprehensive Cancer Center) at Columbia University Vagelos College of Physicians and Surgeons.

“Conversely, patients whose disease is likely to remain confined to the prostate could be spared from getting unnecessary therapy.”

The genes in our signature are not only correlated with metastasis, they appear to be driving metastasis. That means that if that we can suppress the activity of those genes, we might be able to prevent cancer from spreading or at least improve outcomes.

Juan M. Arriaga

The study was published online in Nature Cancer.

Existing Tests Can’t Identify Aggressive Cancers

Prostate cancer is the second-leading cause of cancer death in males in the United States, with an estimated 33,330 men likely to succumb to the disease this year.

With five-year survival rates above 99 percent, most prostate cancers remain limited to the prostate and can be successfully controlled by active surveillance or local therapy (mostly surgery or radiotherapy).

However, if prostate cancer has spread, it is considered incurable, and five-year survival chances are around 30%.

“The problem is that with existing tests, it’s hard to know which cancers are which,” says the study’s lead author, Juan M. Arriaga, Ph.D., an associate research scientist in molecular pharmacology and therapeutics at Columbia University Vagelos College of Physicians and Surgeons.

“We miss a lot of aggressive cancers that should have been treated earlier, and we over-treat some slow-growing cancers that probably would not have spread.”

New Gene Signature First Identified in New Mouse Model

The researchers first created a mouse model of prostate cancer that accurately reflects the human form of the disease, including how cancer spreads to the bone, which is the tissue most commonly affected by prostate cancer metastases, in order to find a more accurate method of predicting advanced prostate cancer.

The researchers observed that bone metastases have a different molecular profile than initial tumors using this first-of-its-kind animal model.

“By focusing on those differences, we were able to identify 16 genes that drive localized prostate cancer to metastasize,” Abate-Shen says.

16 Genes Predict Metastasis in Patients

The META-16 genetic signature was then tested on biopsies from hundreds of patients with locally advanced prostate cancer. The researchers were kept in the dark about the patients’ outcomes.

META-16 was proven to be highly successful at predicting time to metastases and responsiveness to anti-androgen therapy by the Columbia researchers (which is used to suppress androgen, the male hormone, which promotes tumor progression).

The team is currently fine-tuning the test, which they intend to test in a prospective clinical study later this year. META-16 might theoretically be exploited to create therapeutics for metastatic prostate cancer.

“The genes in our signature are not only correlated with metastasis, they appear to be driving metastasis,” Arriaga says. “That means that if that we can suppress the activity of those genes, we might be able prevent the cancer from spreading or at least improve outcomes.”

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