Using a Generic Drug to Starve Pancreatic Cancer Cells

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Using a Generic Drug to Starve Pancreatic Cancer Cells

Researchers have discovered that substituting a key nutrient essential for the survival and growth of pancreatic cancer cells with a generic drug can effectively starve the cancer, slowing down its rate of spread.

This breakthrough opens up new avenues for treating this deadly form of cancer, which has one of the lowest survival rates among all cancers, with an average survival time of just three and a half years, even when detected in the late stages or before spreading. One of the challenges in treating pancreatic cancer lies in its unique characteristics.

Using a Generic Drug to Starve Pancreatic Cancer Cells

In a recent study conducted at the Burnham-Priebys Medical Discovery Institute in California, researchers leveraged the unique properties of pancreatic tumors to halt their growth and spread.

The study’s lead author, Cosimo Commisso, stated, “Pancreatic tumors are often encapsulated within dense connective tissue, isolating them from other parts of the body and cutting off their oxygen supply. As a result, these cancers have distinct metabolic characteristics compared to other tumors, which we can potentially exploit to develop new treatment methods.”

One distinguishing feature of pancreatic cancer is its dependence on the nutrient glutamine. Pancreatic cancer cells rely on glutamine for survival and proliferation. Consequently, the researchers used 6-diazo-5-oxo-L-norleucine (DON) in mice, a substance structurally similar to glutamine but unable to serve as a fuel source. They found that it significantly slowed tumor growth and prevented its spread.

Researchers realized that when glutamine is unavailable, pancreatic cancer cells can turn to other nutrients. To counter this, they combined DON with existing cancer treatment methods to prevent the cells from accessing another crucial nutrient, asparagine.

Commisso explained, “After using DON, cancer cells cannot rely on glutamine, but they can begin depending on other nutrients as a backup, including asparagine. We believe that if we can prevent them from using both glutamine and asparagine, the tumor loses its choices.”

Cells need asparagine to produce proteins and generate new cells, and L-asparaginase is a chemotherapy drug that breaks down asparagine, inhibiting cell division and growth. Researchers observed a synergistic effect when combining DON and L-asparaginase, helping to prevent pancreatic tumors from spreading to other organs.

While DON has undergone early clinical trials as a treatment for lung cancer, and L-asparaginase has begun to be used, this is the first time they have been combined.

Commisso noted, “This is particularly exciting because pancreatic cancer treatment for patients may be relatively straightforward to further explore, as the research framework for other solid tumors already exists. This could change the approach to treating pancreatic cancer, and a significant amount of preclinical work required to rationalize it is already underway.”

This research was published in the journal “Nature Cancer.”