Researchers found that replacing a nutrient that pancreatic cancer cells need to survive and grow with a generic drug starved the cancer, slowing its spread. The discovery opens the door to entirely new ways to treat this deadly cancer. Pancreatic cancer has one of the lowest survival rates. Even if the cancer is caught before it becomes advanced or spreads, the average survival time is only three to three and a half years. One of the challenges in treating pancreatic cancer has to do with the properties of the tumor itself.
In a new study, researchers at the Burnham Prebys Medical Discovery Institute in Stanford, California, exploited the unique properties of pancreatic tumors to halt the cancer's growth and spread.
Cosimo Commisso, the study's corresponding author, said: "Pancreatic tumors are often wrapped in dense connective tissue, insulating them from the rest of the body and cutting off oxygen supply. Therefore, these cancers have unique metabolic properties compared to other tumors, and we may be able to exploit this to develop new treatments."
What sets pancreatic cancer apart from other cancers is its dependence on the nutrient glutamine, which pancreatic cancer cells use to survive and proliferate. So the researchers used 6-diazo-5-oxo-L-norleucine (DON), which is structurally similar to glutamine but cannot be used as a fuel source, in mice and found that it significantly slowed the growth of tumors and prevented their spread.
The researchers realized that when glutamine is unavailable, pancreatic cancer cells can use other nutrients, so they combined DON with existing cancer treatments to prevent the cells from accessing another important nutrient, asparagine.
"With DON, cancer cells can't use glutamine, but they can start to rely on other nutrients as backup, including asparagine," Commisso said. "We thought that if we could prevent them from using glutamine and asparagine, tumors would lose that option."
Cells need asparagine to make proteins and generate new cells, and L-asparaginase is a chemotherapy drug that breaks down asparagine, inhibiting cell division and growth. The researchers observed that combining DON and L-asparaginase produced a synergistic effect that helped prevent pancreatic tumors from spreading to other organs.
Although DON has passed early clinical trials as a treatment for lung cancer and L-asparaginase has also been used, this is the first time that the two have been used together.
"This is particularly exciting because further exploration of treatments for patients with pancreatic cancer may be relatively simple because study designs for other solid tumors already exist," Commisso said. "This could change the way pancreatic cancer is treated, and the extensive preclinical work needed to rationalize it is already underway."
The research was published in the journal Nature Cancer.