Glutamate a Promising New Biomarker for Prostate Cancer Aggressiveness

A team of investigators found that levels of serum glutamate, a naturally occurring nonessential amino acid that plays a key role in cancer metabolism, are increased in patients with primary and metastatic prostate cancer.

In a study involving 366 men, the team measured serum glutamate levels in 60 healthy adult males, 197 with primary prostate cancer and 109 with metastatic castration-resistant prostate cancer—cancer that progresses following androgen depletion therapy. They also reported that the glutamate antagonist riluzole (Rilutek), a well-tolerated oral medicine for depression and ALS, induces cell death while inhibiting the progression and motility of human prostate cancer cells.

The team of investigators from three institutions was led by Shahriar Koochekpour, MD, PhD, associate professor of cancer genetics, urology, and oncology in the Roswell Park Cancer Institute (RPCI; Buffalo, NY, USA) department of cancer genetics. “Comparing normal, primary and metastatic prostate cancer tissues, we discovered that glutamate receptor is expressed at very high levels in primary and metastatic tumors, but at very weak or undetectable levels in benign prostate tissues.” noted Prof. Koochekpour “And serum glutamate was detected at increased levels proportional to Gleason score, the standard index for rating prostate cancer aggressiveness and prognosis in patients with primary tumors.”

“We detected one major difference between African-Americans and Caucasians in the study,” Dr. Koochekpour notes. “In African-Americans, serum glutamate levels were higher among those men with metastatic disease than in those with primary prostate cancer, and we didn’t see that trend in Caucasian men. This finding may implicate a role for glutamate metabolism in inter-racial disparities of prostate cancer.”

Dr. Koochekpour and colleagues are currently conducting a preclinical study assessing the effectiveness of riluzole in preventing growth of human prostate cancer cells in animal models, and hope to build on these results in the clinical setting within the next 12-18 months.

The mission of the Roswell Park Cancer Institute is to understand, prevent, and cure cancer. Founded in 1898, RPCI was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York.

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Roswell Park Cancer Institute