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Researchers shed light on metabolic changes in pancreatic cancer cells
Alec Kimmelman, MD, PhD, recipient of a Career Development Award from the Pancreatic Cancer Action Network in 2010, was co-senior author of a recent article in the prominent scientific journal Nature. Dr. Kimmelman undertook these studies at Dana-Farber Cancer Institute, with collaboration from researchers there and at several other institutions. Among the other authors on the paper are Nabeel Bardeesy, PhD, recipient of the 2008 Randy Pausch, PhD – Pancreatic Cancer Action Network – AACR Career Development Award, and Jason Fleming, MD, member of our Medical Advisory Board.
An important goal of cancer research is to identify ways in which cancer cells behave differently from normal cells, especially in regard to the growth and survival of the cells. One of the challenges in devising new treatment strategies for cancer is that the cancer cells too closely resemble normal cells. Therefore, determining the differences between cancer and normal cells can reveal vulnerabilities that can be therapeutically targeted in the cancer cells, causing little to no toxicity to normal cells.
Cancer cells and normal cells have been shown to differ in their ability to metabolize, or break down, nutrients. In previous work, Dr. Kimmelman and others have reported that pancreatic cancer cells break down sugar in a unique manner (see summary here). In this new Nature paper, Dr. Kimmelman and colleagues looked at the mechanism by which pancreatic cancer cells metabolize the amino acid glutamine. Amino acids are the building blocks of proteins, and glutamine is a prevalent amino acid. The breakdown of glutamine produces energy and molecular materials that are then used to make new proteins and other critical molecules in the cell, including parts of DNA.
The research team revealed that pancreatic cancer cells break down glutamine in a manner that is unique from normal cells. Furthermore, the study shows that pancreatic cancer cells are quite dependent on glutamine as a source of energy. In analyses of cells in a dish and pancreatic cancer cells implanted into mice, the researchers discovered that blocking key proteins in the cellular process by which glutamine is metabolized slowed or stopped the growth of pancreatic cancer cells. Importantly, blocking this process had no effect on healthy cells from the pancreas.
The tools that were used to block the glutamine metabolism process in the laboratory cannot be used in human patients. However, the data presented in this paper suggest that blocking pancreatic cancer cells’ ability to break down glutamine could be a beneficial treatment strategy. Moreover, even if the cells survive glutamine metabolism inhibition, they are left more vulnerable to conventional treatments, like chemotherapy or radiation. The results presented in this paper will require more laboratory experimentation before testing in a clinical trial setting could take place. These elegant studies could pave the way for a novel approach of blocking the growth of pancreatic cancer cells, while sparing normal cells.
