Replacing a critical nutrient with a mimic starves pancreatic cancer
Researchers have found that replacing a nutrient that pancreatic cancer cells rely on to survive and grow with a copycat version starves the cancer, slowing its spread. The finding opens the door to an entirely new approach to treating this deadly type of cancer.
Pancreatic cancer has one of the lowest survival rates of all cancers. Even if the cancer is caught before it becomes too advanced or spreads, the average survival time is only three to three-and-a-half years. One of the challenges of treating pancreatic cancer has to do with the properties of the tumors themselves.
In a new study, researchers at Stanford Burnham Prebys Medical Discovery Institute, California, exploited the unique properties of pancreatic tumors and used them to halt the cancer’s growth and spread.
“Pancreatic tumors tend to be packed in dense connective tissue that keeps them encapsulated from the rest of the body and cuts off their supply of oxygen,” said Cosimo Commisso, corresponding author of the study. “As a consequence, these cancers develop unique metabolic properties compared to other tumors, and this is something we may be able to exploit with new treatments.”
One thing that sets pancreatic cancer apart from other cancers is its reliance on the nutrient glutamine, which its cells use to survive and proliferate. So, in mice the researchers used 6-Diazo-5-oxo-L-norleucine (DON), which is structurally similar to glutamine but can’t be used as a fuel source, and found that it significantly slowed tumor growth and stopped its spread.
Aware that pancreatic cancer cells can use other nutrients when glutamine’s not available, the researchers combined DON with an existing cancer treatment to block the cells’ access to another important nutrient, asparagine.
“With DON, the cancer cells can’t use glutamine, but they can start to depend on other nutrients as a backup, including asparagine,” Commisso said. “We thought that if we could stop them from using glutamine and asparagine, the tumors would run out of options.”
Cells need asparagine to make proteins and create 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, helping prevent the spread of pancreatic tumors to other organs.
While DON has been through early clinical trials as a lung cancer treatment, and L-asparaginase is already being used, this is the first time the two have been used together.
“This is particularly exciting because exploring it further for pancreatic cancer patients could be relatively simple since the study designs exist for other solid tumors,” said Commisso. “This could be a game changer for pancreatic cancer, and a lot of the preclinical work needed to rationalize it is already happening.”
The study was published in the journal Nature Cancer.
Source: Stanford Burnham Prebys