Pancreatic cancer manages to change diet to survive – 05/23/2023 – Equilibrium and Health

Pancreatic ductal adenocarcinoma (PDA) is one of the cancers with the highest mortality rate in the world. Part of the problem lies in the late diagnosis, since the disease does not lead to the appearance of signs and symptoms in the early stages. The other part is related to resistance to therapy, a puzzle that, last week, gained a new piece, described in an article published in the journal Nature.

In the text, 29 researchers from the universities of Michigan, Chicago and Washington in St. Louis, in the United States, and the Cancer Research Institute (ICR), in England, show that cells of this type of tumor are able to change their source of energy when glucose is not available.

According to the group, in a scenario of lack of sugar, there is the use of uridine present in the tumor microenvironment. This is possible because an enzyme known as uridine phosphorylase-1 breaks uridine into two parts, including a different form of sugar, ribose. This alternative guarantees the survival and proliferation of tumor cells.

In the analysis of the scientists invited by Nature to evaluate the article —the so-called peer review—, the research cannot be considered unprecedented because previous studies already pointed to the use of uridine in contexts of glucose deprivation, but it is important for demonstrating its use in the PDA.

The researchers started from the impact of 175 possible nutrients on 21 cell lines in a glucose-restricted environment. They looked at how nutrients were used by tumor cells over time and, from the results, turned their attention to uridine.

The main criterion for the sieve was the correlation between nutrient utilization patterns by cells and the expression of genes associated with these compounds. In the case of uridine, they observed a direct link with the UPP1 gene, which encodes uridine phosphorylase-1.

In addition, the team found that, although at different levels, all cell lines tested used uridine, suggesting that it is a widely used metabolic fuel. Also noteworthy was the fact that, contrary to expectations, cells use a nucleoside (formed by a sugar and a nitrogenous base), and not carbohydrates, and that this is a process not yet explored in the context of PDA.

Having defined the metabolite, the group began a series of tests. In one of them, carried out with mice, the team found that blocking UPP1 prevented the use of uridine by cancer cells and stopped tumor growth.

“As a next step, we will explore ways to use uridine to monitor existing therapeutic responses in pancreatic cancer and hopefully develop new drugs targeting UPP1,” said Anguraj Sadanandam, one of the study’s authors, in the note released by the ICR.

“We hope that our research efforts will lead to new treatment strategies for people diagnosed with pancreatic cancer,” he added.