Targeting Cellular Energetics via Ferroptosis Mediated Cell Death in Resistant Colorectal Cancer Stem Cells

Ferroptosis, a newly discovered non-apoptotic form of cell death triggered by iron-dependent toxic membrane lipid peroxidation, establishes a link between redox biology, metabolism, and human health. By inducing ferroptosis, it is possible to selectively eliminate cancer cells and cancer stem cells (CSCs) that are resistant to traditional therapies. Recent research has shown that inducing ferroptosis can effectively kill colorectal cancer stem cells (CRC CSCs) that are resistant to other forms of cell death and treatment modalities, positioning it as a potentially innovative strategy for developing treatments for colorectal cancer. This review delves into the intricate molecular mechanisms underlying ferroptosis in colorectal CSCs, focusing on the specific pathways and signaling networks that regulate ferroptotic cell death in these cells, including the roles of iron metabolism, lipid peroxidation, amino acid metabolism, and antioxidant systems. Additionally, we explored the application of ferroptosis-associated genes for the early diagnosis and prognosis of CRC and also discuss ferroptosis inducers as anticancer agents, highlighting their potential to effectively target therapy-resistant CSCs by disrupting their redox balance and triggering lipid peroxidation. Last, we discuss potential challenges and directions for future research in this developing area, offering insights into future studies pertaining to ferroptosis in CRC treatment.