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Glutamine Ratio Is Key Ovarian Cancer Indicator

Researchers find link to cancer biomarker

An analysis of the metabolic profiles of hundreds of ovarian tumors has led to a new test to determine whether ovarian cancer cells have the potential to metastasize. The study, led by researchers at Rice University, also suggests how ovarian cancer treatments can be tailored based on the metabolic profile of a particular tumor, according to an article that will appear this week in Molecular Systems Biology.

“We found a striking difference between the metabolic profiles of poorly aggressive and highly aggressive ovarian tumor cells, particularly with respect to their production and use of the amino acid glutamine,” said lead researcher Dr. Deepak Nagrath.

According to Nagrath, the new metabolic analysis indicates that ovarian cancer may be susceptible to multidrug cocktails, particularly if the amounts of the drugs can be tailored to match the metabolic profile of a patient’s tumor.

The research also revealed a specific biochemical test that pathologists could use to guide such treatments. The test involves measuring the ratio between the amount of glutamine that a cell takes up from outside and the amount of glutamine it makes internally.

“This ratio proved to be a robust marker for prognosis,” said co-author Professor Anil Sood. “A high ratio was directly correlated to tumor aggression and metastatic capability. Patients with this profile had the worst prognosis for survival.”

The 3-year study included cell culture studies at Rice as well as an analysis of gene-expression profiles of more than 500 patients from the Cancer Genome Atlas and protein-expression profiles from approximately 200 MD Anderson patients.

According to Nagrath, the study revealed a key finding — a direct relationship between glutamine and the ovarian cancer biomarker STAT3.

“The higher STAT3 is, the more aggressive the cancer,” he said. “For the first time, we were able to show how glutamine regulates STAT3 expression through a well-known metabolic pathway called the TCA cycle, which is also known as the Krebs cycle.”

Nagrath said the research is ongoing. Ultimately, he hopes the research will lead to new treatment regimens for cancer as well as a better understanding of the role of cancer-cell metabolism in metastasis and drug resistance.

Source: Rice University; May 5, 2014.

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