Study Finds Cancer Cells Use Uridine as a New Fuel Source in the Absence of Sugar: Insights into Metabolic Processes and Therapeutic Pathways for Pancreatic Cancer
Researchers at the University of Michigan Rogel Cancer Center have made a groundbreaking discovery that could lead to new therapeutic pathways for pancreatic cancer. The study, published in the prestigious scientific journal Nature, reveals that cancer cells can adapt to limited glucose intake by using a new nutrient source - uridine.
Pancreatic tumors have few functioning blood vessels and therefore cannot easily access nutrients that come from the bloodstream, such as glucose. This means that cancer cells must find alternative ways to obtain the nutrients they need to survive and grow. Previous studies have identified other nutrients that serve as fuel sources for pancreatic cancer, including glutamine and fatty acids. However, this study adds uridine to the catalog of nutrient sources that cancer cells can use to adapt to nutrient deprivation.
Uridine is a molecule that is essential for the synthesis of RNA, a key component of the genetic machinery in cells. While uridine is present in the tumor microenvironment, the exact source of uridine and how cancer cells access it remain unclear. The researchers speculate that cancer cells may sense the concentrations of glucose and uridine in the local environment to inform their adaptation.
The study, led by Dr. Costas Lyssiotis, Maisel Research Professor of Oncology, used a technology that screened hundreds of different nutrients to see which ones support pancreatic cancer growth. This method led them to discover uridine, which offers therapeutic insight as it is metabolized by the enzyme uridine phoshorylase-1 (UPP1). Blocking UPP1 had a major impact on the growth of pancreatic tumors in mice, suggesting the importance of testing drugs that block uridine as a possible new treatment option.
The researchers found that cancer cells can use uridine as a fuel source when they don't have access to glucose. The team recognizes two ways that cancer cells control their usage of uridine: an unknown regulatory process and a cancer-promoting mutation in the KRAS gene, which is common in pancreatic cancer.
Dr. Zeribe Nwosu, one of the co-first authors of the study, said, "The ability of cancer to switch to alternative nutrients has fascinated me for a long time. Blocking such compensatory switches could lead us to new treatments and that's the door we hope this study will open."
Dr. Lyssiotis and his team have been working on this research for nearly a decade alongside their collaborators in the Sadanandam lab at the Institute for Cancer Research in London. The discovery of uridine as a fuel source offers new avenues for research into the mechanisms of cancer cell adaptation and the development of new treatments for pancreatic cancer.
"The findings offer potential for better understanding and treating pancreatic cancer with new drug targets and therapeutic approaches," said Dr. Sadanandam, co-author on the study. However, more research is needed to determine the best way to move this discovery to the clinic.
Overall, this study provides a fascinating insight into the adaptive nature of pancreatic cancer cells and the potential for new treatment options for this challenging disease. The discovery of uridine as a fuel source offers hope for patients and their families, and the tireless work of researchers in this field continues to offer new hope for cancer patients around the world. By targeting the metabolic processes of cancer cells, we may be able to develop more effective and personalized therapies for this devastating disease.