RRM1 gene may better predict survival for pancreatic adenocarcinoma

Moffitt Cancer Center researchers have identified a gene that may better predict survival for pancreatic adenocarcinoma, the fourth leading cause of cancer deaths in the United States. Researcher Richard Kim, M.D., assistant member of the Experimental Therapeutics Program and colleagues from several other research institutions conducted a study that better defines the role of ribonucleotide reductase M1 (RRM1). The RRM1 gene encodes the regulatory subunit of ribonucleotide reductase, the molecular target of gemcitabine, a commonly used chemotherapy in pancreatic cancer.

In the study, which appeared in the Jan. 1 issue of Cancer, the research team investigated the therapeutic predictive value of RRM1 expression for the chemotherapy drug gemcitabine. They found that for patients with pancreatic adenocarcinoma removed by surgery, low RRM1 expression predicted an overall survival benefit with gemcitabine therapy. High RRM1 expression predicted benefit from non-gemcitabine therapy.

"We previously hypothesized that low expression of RRM1 could predict the treatment success of gemcitabine," Kim said. "This study was carried out to determine whether RRM1 expression correlates with better survival for patients receiving gemcitabine therapy."

The retrospective study included 122 patients who had undergone surgery for pancreatic adenocarcinoma from 1999 to 2007. In the subgroup of patients who received gemcitabine therapy, those with low RRM1 expression had longer overall survival and a trend toward progression-free survival. Those patients with high RRMI expression who received non-gemcitabine therapy had significantly longer overall survival and progression-free survival.

"Our findings indicate that to achieve the best survival after surgical resection, the level of RRM1 expression may be used to select which patients receive gemcitabine therapy and which do not," Kim said.

The authors noted that their findings were consistent with similar studies on the role RRM1 plays in chemotherapy for patients with non-small cell lung cancer, yet their conclusions "should be interpreted with caution" due to their small sample size and the therapeutic success of non-gemcitabine therapies after surgery.

"A validation study should be carried out before the current findings can be clinically applied," Kim added.


Moffitt Cancer Center


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