Replacing a critical nutrient with an antagonist substitute starves pancreatic cancer

Good news! Cancer is history (soon)! Looks like a very elegant solution.

"Pancreatic cancer is relatively rare, accounting for only 3% of all cancers. However, it has one of the lowest survival rates among cancers: most people only live three to six months after being diagnosed with this disease."

"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. ...

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. ...
the researchers combined DON with an existing cancer treatment to block the cells’ access to another important nutrient, asparagine. ...
The researchers observed that combining DON and L-asparaginase produced a synergistic effect, helping prevent the spread of pancreatic tumors to other organs. ..."

From the abstract:

"In pancreatic ductal adenocarcinoma (PDAC), glutamine is a critical nutrient that drives a wide array of metabolic and biosynthetic processes that support tumor growth. Here, we elucidate how 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist that broadly inhibits glutamine metabolism, blocks PDAC tumor growth and metastasis. We find that DON significantly reduces asparagine production by inhibiting asparagine synthetase (ASNS), and that the effects of DON are rescued by asparagine. As a metabolic adaptation, PDAC cells upregulate ASNS expression in response to DON, and we show that ASNS levels are inversely correlated with DON efficacy. We also show that L-asparaginase (ASNase) synergizes with DON to affect the viability of PDAC cells, and that DON and ASNase combination therapy has a significant impact on metastasis. These results shed light on the mechanisms that drive the effects of glutamine mimicry and point to the utility of cotargeting adaptive responses to control PDAC progression."

Replacing a critical nutrient with a mimic starves pancreatic cancer (secondary news source)

Copycat nutrient leaves pancreatic tumors starving (primary news source)

Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma (no public access)