Chemotherapy-synthetic Compound Combo may Lead to Better Pancreatic Cancer Therapy

Researchers at UT Southwestern Medical Center found chemotherapy in combination with a synthetic compound- JP1201- which mimics the action of a naturally occurring "death-promoting" protein found in cells, can dramatically reduce human pancreatic cancer cells.

The research, conducted in mice, could lead to more effective therapies for pancreatic and possibly other cancers, said the researchers.

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"This compound enhanced the efficacy of chemotherapy and improved survival in multiple animal models of pancreatic cancer. We now have multiple lines of evidence in animals showing that this combination is having a potent effect on pancreatic cancer, which is a devastating disease," said Dr. Rolf Brekken, associate professor of surgery and pharmacology and the study's senior author.

In the study, the researchers transplanted human pancreatic tumours into mice, then allowed the tumours to grow to a significant size.

They then administered a synthetic compound called JP1201 in combination with gemcitabine, a chemotherapeutic drug that is considered the standard of care for patients with pancreatic cancer.

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They found that the drug combination caused regression of the tumours.

"There was a 50 percent regression in tumour size during a two-week treatment of the mice. We also looked at survival groups of the animals, which is often depressing in human therapeutic studies for pancreatic cancer because virtually nothing works. We found not only significant decrease in tumour size, but meaningful prolongation of life with the drug combination," said Brekken.

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The drug combination was also effective in an aggressive model of spontaneous pancreatic cancer in mice.

JP1201 was created in 2004 by UT Southwestern researchers to mimic the action of a protein called Smac.

Smac was discovered in 2000 and was found to play a key role in the normal self-destruction process present in every cell.

Cell death, or apoptosis, is activated when a cell needs to be terminated, such as when a cell is defective or is no longer needed for normal growth and development.

In cancer cells, this self-destruct mechanism is faulty and lead to breaks in the cell-death cascade of events.

The synthetic Smac, or Smac mimetic, developed at UT Southwestern inhibits these breaks, allowing the cell to die.

"In essence, we're inhibiting an inhibitor. And we're allowing the apoptotic cascade to kick off, resulting in the death of cancer cells," said Brekken.

The study has been published in the latest issue of Cancer Research.

Source-ANI
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