New Solution for Treating Intractable Cancer with 'Feroptosis'

Elucidation of a Novel Cell Death Pathway Based on Unsaturated Fatty Acid Synthesis
Expected to Greatly Contribute to the Development of Treatments for Intractable Cancers

[Photo by Yangji Hospital]

[Asia Economy Reporter Junho Hwang] A new anticancer treatment method for refractory gastric cancer has been proposed by domestic researchers. This treatment method applies a new cell death principle called ferroptosis to cancer cells. It is expected to contribute to opening a new chapter in the treatment of refractory cancers in the future. On the 13th, the Korea Research Institute of Bioscience and Biotechnology announced the joint research results of the research teams led by Dr. Sangcheol Lee and Dr. Eunwoo Lee from the Metabolic Control Research Center, Dr. Geumsook Hwang’s team, and Professor Yongmin Heo from Yonsei University College of Medicine. The research results were recently published in the Proceedings of the National Academy of Sciences of the United States of America, an international academic journal.

Ferroptosis Enables Treatment of Refractory Cancer

Polyunsaturated Fatty Acid Synthesis Pathway and Ferroptosis Cell Death Mechanism Induced by Lipid Peroxidation

The research team focused on ferroptosis, which refers to iron-dependent necrotic cell death induced by lipid peroxidation of the cell membrane. In normal cells, toxicity is alleviated through a pathway that reduces lipid peroxides to lipid alcohols. Recently, it has attracted attention as an effective cell death pathway applicable to the treatment of refractory cancers that show resistance to anticancer drugs. Lipid peroxidation is a phenomenon in which unsaturated fatty acids in the cell membrane are destroyed by reactive oxygen species, recognized as a cause of cell death.

Based on transcriptome information from gastric cancer patients, the research team classified gastric cancer cell lines into mesenchymal and epithelial types and confirmed that only the mesenchymal type died due to ferroptosis-inducing drugs. They further analyzed that this phenomenon was the result of genes (ELOVL5, FADS1) discovered in this study playing an essential role in forming phospholipids critical for ferroptosis progression in mesenchymal-type gastric cancer cell lines. These genes create an environment conducive to lipid peroxidation, proving that mesenchymal-type gastric cancer cells can be eliminated.

Mesenchymal-type gastric cancer is known as the most prognostically poor cancer, characterized by easy metastasis and resistance to existing anticancer drugs. The 5-year survival rate is below 30%. Mesenchymal cells are a type of stem cell differentiated from the mesoderm formed by the division of a fertilized egg. They have the ability to self-replicate and differentiate into various cell types.

Contributes to Discovery of New Targets for Refractory Disease Treatment

Dr. Eunwoo Lee (right)

Professor Yongmin Heo, co-corresponding author of the study, said, "The refractory disease treatment drugs developed through this research outcome are expected to be effective against refractory gastric cancer, which cannot be prevented from recurring by existing standard anticancer drugs," adding, "It could serve as a model for metabolic drug development." Dr. Eunwoo Lee stated, "We revealed the importance of the unsaturated fatty acid synthesis pathway in the new cell death mechanism called ferroptosis," and added, "The newly discovered genes (ELOVL5 and FADS1) could be important clues for predicting anticancer drug responsiveness." Dr. Geumsook Hwang said, "The lipidomics and metabolic tracing technologies used to elucidate the unsaturated fatty acid synthesis pathway in this research will play a key role in discovering new therapeutic targets for refractory diseases in the future."

This content was produced with the assistance of AI translation services.