Study highlights potential of ferroptosis-based approaches to treat cancer

Therapies that target the utilization of fat by tumors and activate a type of cell death dependent on fat molecules may be a promising avenue to treat cancer, according to new research by UTHealth Houston.

The findings were published today in Trends in Cancer and were co-led by Daniel E. Frigo, PhD, professor at The University of Texas MD Anderson Cancer Center and a faculty member at The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences.

Researchers came to the conclusion through a review of 121 outside studies that examined the relationship between lipid metabolism and progression of various types of carcinoma, a cancer that starts in the tissue lining of the skin. 

"Lipids can make cancers more aggressive," said co-principal investigator Mikhail Kolonin, PhD, director of the Center for Metabolic and Degenerative Diseases in The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at McGovern Medical School at UTHealth Houston. "However, there is a lipid-dependent mechanism that can be activated to fight cancer." 

Lipids are the various types of fat molecules integral to a person's health. As cancer cells and fat tissue, which temporarily store lipids, communicate with each other, tumors can use lipids to grow or spread. But while body fat can support cancer progression, it can also cause a type of cell death known as ferroptosis.

Ferroptosis occurs when lipid peroxides build up on cell membranes. Lipid peroxides are made through the body's normal activities, but when too many accumulate, they can become toxic.

Common cancer treatments like chemotherapy and radiation kill cancer cells by forcing the cells to undergo a different type of cell death. However, certain types of cancers can become resistant to common treatments. 

Understanding the interaction between lipids and tumors can pave the way for cancer therapies that target ferroptosis-inducing chemicals and suppress a tumor's utilization of lipids, Kolonin said. 

"The implication is that there are certain therapeutic approaches that could be potentially developed to target specific mechanisms responsible for lipid processing by the tumors," said Kolonin, who is also the Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research at McGovern Medical School. 

Kolonin said the review also highlights the importance of work at the Center for Metabolic and Degenerative Diseases that seeks to determine the role of cell aging on cancer progression and cachexia, or unintentional weight loss that is induced by some types of tumors.

Additional authors with UTHealth Houston include Hong Anh Cao and Joseph Rupert, PhD. Kolonin is a faculty member at MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences. 

The study was in part supported by the Bovay Foundation and the Levy-Longenbaugh Fund.