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Scientists make pancreatic cancer susceptible to failed drug

Although cancer cells adjust to TRAIL making the drug far less effective, pairing it with another agent allowed it to kill tumor cells.

By Stephen Feller

PHILADELPHIA, April 18 (UPI) -- Researchers in Philadelphia found a method to eliminate the resistance of pancreas cancer to some failed drugs, according to a recent study.

By blocking the protein Hu antigen R, or HuR, the researchers helped a naturally-occurring substance, previously thought to be ineffective, target and kill cancer cells, according to a study published in the journal Molecular Cancer Research,

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The compound, tumor necrosis factor-rlated apoptosis inducing ligand, or TRAIL, was thought to activate a "death receptor" on the surface of cancer cells -- and did so in tests with animals. But in tests with humans it did not have a long-lasting effect because as cells were exposed to it, they expressed higher levels of HuR and survived.

In the new study, researchers at Thomas Jefferson University found blocking HuR increased efficacy of the drug.

"Although these results will not change treatment options for patients today, they give us a glimmer of hope that we can salvage therapies that have already advanced to human clinical trials and are therefore closer to human use than novel therapies," Carmella Romeo, a doctoral student at Thomas Jefferson University, said in a press release.

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For the study, researchers first identified the HuR stress-response protein keeping cells alive by decreasing the number of death receptors on cell surfaces.

When the researchers then treated cancer cells with a drug called MS-444, which is known to inhibit HuR, the number of death receptors increased -- as did the efficacy of TRAIL.

"We've teased out one mechanism behind pancreatic cancer cells' resistance to certain drugs," said Dr. Jonathan Brody, a researcher at the Sidney Kimmel Cancer Center at Thomas Jefferson University. "Knocking out this resistance mechanism could make pancreatic cancer vulnerable to therapies that had great promise in the past. While there's more work to be done to confirm the results in pre-clinical models and then humans, we are encouraged by these preliminary results."

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