by Van Andel Research Institute

Lipid limitation decreases levels of storage lipids and increases levels of some PUFA-containing PEs and PCs. Credit: Cell Chemical Biology (2024). DOI: 10.1016/j.chembiol.2024.09.008

Cutting off cancer cells' access to fat may help a specific type of cancer treatment work more effectively, reports a study by Van Andel Institute scientists. 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.

Corresponding author Dr. Evan Lien and first author Kelly Sokol in the lab at Van Andel Institute. Credit: Van Andel Institute

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."

More information: Kelly H. Sokol et al, Lipid availability influences ferroptosis sensitivity in cancer cells by regulating polyunsaturated fatty acid trafficking, Cell Chemical Biology (2024). DOI: 10.1016/j.chembiol.2024.09.008

Journal information: Cell Chemical Biology 

Provided by Van Andel Research Institute