Oncology & Cancer

Study indicates that in the absence of sugar, cancer cells employ a new fuel source.

A new source of nutrients that pancreatic cancer cells use to grow has been discovered by researchers at the University of Michigan Rogel Cancer Center. The particle uridine offers insight into both biochemical cycles and conceivable remedial pathways.

Cancer cells can adapt when they don’t have access to glucose, according to the Nature article. Other nutrients that pancreatic cancer uses as fuel have already been found by researchers; this study adds uridine to the index.

Pancreatic growths have few working veins and can only, with significant effort, access supplements that come from the circulation system, similar to glucose. According to Costas Lyssiotis, Ph.D., the study’s principal investigator and Maisel Research Professor of Oncology, cancer cells become hungry when they do not receive the appropriate nutrients. Of course, they continue to grow, but how do they do so? He stated, These findings demonstrate that uridine is one of those fuels in certain circumstances.”

“I’ve been captivated by the potential of cancer to switch to other nutrition for a very long time. We anticipate that this work will open the door to novel treatments by blocking such compensating changes.”

 Zeribe Nwosu, Ph.D., one of the co-first authors in the study,

I’ve got some information about the effect, Zeribe Nwosu, Ph.D., one of the co-first creators in the review, says, “The capacity of disease to change to elective supplements has captivated me for quite a while. “Hiding such compensatory switches could lead us to new medicines, and that is the entryway we trust this study will open.”

Uridine can be found in the tumor microenvironment, but no one knows where it comes from or how cancer cells get to it. Some portion of the image is that it’s in the circulatory system, yet we don’t have the foggiest idea where it’s coming from explicitly,” said Lyssiotis. “We haven’t been able to pinpoint a single source, so it probably comes from multiple places.”

Occasions that Lyssiotis alludes to as “seasons of emergency”—when cells need more supplements in light of restricted blood access as well as extraordinary rivalry between cells — could be a hint with respect to why and where cells go to uridine. “The malignant growth cells appear to be detecting the centralization of glucose and uridine in the neighborhood climate to illuminate their transformation,” says Matt Ward, another co-first creator. The team led by Lyssiotis recognizes this unidentified regulatory mechanism as well as a KRAS gene mutation that promotes cancer and is prevalent in pancreatic cancer as two ways that cancer cells control how they use uridine.

Lyssiotis and his team, along with their colleagues in the Sadanandam lab at the Institute for Cancer Research in London, have been working on this research for nearly a decade. To determine which nutrients support the growth of pancreatic cancer, they made use of a technology that screened hundreds of different nutrients. Normally, researchers look at common nutrients like sugar, protein, and fat; however, the team led by Lyssiotis took a different approach.

“We utilized a huge board with north of 20 pancreatic cell lines and around 200 distinct supplements to survey various ways pancreatic disease cells develop,” he made sense of. “What exactly do they metabolize? We discovered uridine thanks to this approach.”

In addition, this method provides therapeutic insight. The results demonstrated that the enzyme uridine phoshorylase-1, or UPP1, is responsible for metabolizing uridine. Hindering UPP1 significantly affected the development of pancreatic cancers in mice, a discovery that proposes the significance of testing drugs that block uridine as conceivable new therapy choices.

Sadanandam, a co-author on the study, stated, “There is potential to better understand and treat pancreatic cancer with new drug targets and therapeutic approaches.”

More examination is expected to determine the most effective way to move this revelation to the center.

More information: Zeribe C. Nwosu et al, Uridine-derived ribose fuels glucose-restricted pancreatic cancer, Nature (2023). DOI: 10.1038/s41586-023-06073-w

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