New research by the Langney Health Center of New York University in the United States found that a new drug combination safely restricted the growth of pancreatic cancer in mice by preventing cancer cells from obtaining fuel. The relevant paper was published online on the 9th in the journal Nature Cancer. The findings reveal how pancreatic cancer cells can find alternative sources of fuel to avoid hunger and maintain growth. As oxygen, blood sugar, and other resources supplied by blood become scarce, rapidly growing pancreatic tumors become increasingly dense, cutting off their own blood supply. In this environment, the ability to convert "fuel" leads to the lethality of pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) cells use glutaminase to convert amino acid glutamate into glutamine, which can be used as a fuel to maintain rapid tumor growth. The new drug combination aims to prevent this transformation of PDAC cells. DRP-104 is a tumor targeting precursor drug that mimics glutamine to starve cancer cells, which widely inhibits all metabolic pathways that use glutamine. In the current study, DRP-104 alone can reduce the growth rate of PDAC in the pancreatic cancer mouse model. Importantly, the research team also found that DRP-104 leads to a metabolic crisis in PDAC cells. However, PDAC cells increase signal transduction through a protein called extracellular signal-regulated kinase (ERK), which can compensate for the loss of glutamine metabolism. When the team used DRP-104 in combination with trimetinib, an existing drug that blocks ERK signaling pathway, compared with DRP-104 alone, it further improved the survival rate of pancreatic cancer mouse model. Researchers indicate that these drugs have been clinically tested and, if proven effective, may ultimately improve patient treatment outcomes. In the future, the research team will understand how the antagonism of glutamine affects the clearance mechanism of other adaptive nutrients in pancreatic cancer, and whether these mechanisms can also become therapeutic targets. [Editor in Chief Circle] Cancer cells require significantly different nutrients and metabolic pathways from normal cells, so the medical community has long wanted to starve cancer cells by changing their nutritional environment. But cancer cells are very cunning and tenacious, they can adapt to harsh environments, can still sleep, and once the wind blows, they jump out and commit crimes. Therefore, it is not yet possible to simply "wean" the tumor. However, through experimental exploration, we have been able to reverse the trend of tumor growth in many specific scenarios. Hunger will not kill it, but also make it lean. Reporter: Zhang Jiaxin (Xinhua News Agency)
Edit：GuoGuo Responsible editor：FangZhiYou
Source：people.cn
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