Starving cancer cells of fat may improve cancer treatment

The findings, published in Cell Chemical Biology, lay the groundwork for developing tailored dietary strategies to help anti-cancer medications better kill malignant cells.

"We want to make cancer treatment more effective," said Evan Lien, Ph.D., an assistant professor at VAI and the study's corresponding author. "The best way to do this is by understanding how cancer cells behave and identifying ways to break through their defenses. Our findings are an important step toward evidence-based diets that could one day augment existing therapies."

Fats are critical nutrients required for healthy function. Cancer cells hijack normal cellular processes and steal resources like fats, which then act as fuel for sick cells to grow and spread.

The study focused on ferroptosis, a type of cell death that occurs when fat molecules in cancer cells experience damage. In recent years, targeting ferroptosis has emerged as an increasingly promising avenue for developing new anti-cancer strategies.

Many of the mechanisms that enable cancer cells to grow uncontrollably also allow them to avoid cellular quality control processes that usually kill and remove sick cells. Ferroptosis can be an exception, which makes it a potentially powerful tool to leverage in cancer treatment.

Using cell models, Lien and his team showed that removing cancer cells' access to fats makes them highly sensitive to ferroptosis and, by extension, drugs that induce ferroptosis.

The findings are promising, Lien says, but much more work is needed to replicate the discovery in other models of cancer. He and his team also are investigating if the type and amount of fat can be manipulated through diet to make ferroptosis inducers work more effectively.

"Diet is something that's relatively easy to modify," Lien said. "We're not there yet, but the thing we're most excited about is how we might be able to use what we learn to one day design diets tailored to different types of treatment. That could be transformative."

Authors include Kelly H. Sokol, Cameron J. Lee, Thomas J. Rogers, Ph.D., Althea Waldhart, Abigail E. Ellis, Samuel R. Daniels, Rae J. House, Ph.D., Xinyu Ye, Mary Olsenavich, Amy Johnson, Benjamin R. Furness, and Ryan D. Sheldon, Ph.D. of VAI; and Sahithi Madireddy of the Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology.