Harnessing Ferroptosis to Overcome Drug Resistance in Colorectal Cancer: Promising Therapeutic Approaches

SIMPLE SUMMARY: In the realm of colorectal cancer treatment, drug resistance is a formidable obstacle. However, a ray of hope emerges in the form of ferroptosis, a unique iron-driven cell death mechanism. This review delves into the role of ferroptosis in colorectal cancer and its implications for drug resistance. Unlike conventional cell death pathways, such as apoptosis and necrosis, ferroptosis offers distinct advantages. We explore current research breakthroughs, including innovative strategies like ferroptosis inducers, iron metabolism and lipid peroxidation interventions, and combination therapies. Additionally, we investigate the potential of immunotherapy in modulating ferroptosis. While targeting ferroptosis presents notable strengths, it comes with challenges in specificity and drug development. Looking ahead, this review underscores the promise of ferroptosis-based therapies in colorectal cancer and emphasizes the need for ongoing research to unlock its full potential, offering renewed hope for colorectal cancer patients. ABSTRACT: Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, the emerging field of ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation, has offered new insights and potential therapeutic strategies for overcoming drug resistance in CRC. This review examines the role of ferroptosis in CRC and its impact on drug resistance. It highlights the distinctive features and advantages of ferroptosis compared to other cell death pathways, such as apoptosis and necrosis. Furthermore, the review discusses current research advances in the field, including novel treatment approaches that target ferroptosis. These approaches involve the use of ferroptosis inducers, interventions in iron metabolism and lipid peroxidation, and combination therapies to enhance the efficacy of ferroptosis. The review also explores the potential of immunotherapy in modulating ferroptosis as a therapeutic strategy. Additionally, it evaluates the strengths and limitations of targeting ferroptosis, such as its selectivity, low side effects, and potential to overcome resistance, as well as challenges related to treatment specificity and drug development. Looking to the future, this review discusses the prospects of ferroptosis-based therapies in CRC, emphasizing the importance of further research to elucidate the interaction between ferroptosis and drug resistance. It proposes future directions for more effective treatment strategies, including the development of new therapeutic approaches, combination therapies, and integration with emerging fields such as precision medicine. In conclusion, harnessing ferroptosis represents a promising avenue for overcoming drug resistance in CRC. Continued research efforts in this field are crucial for optimizing therapeutic outcomes and providing hope for CRC patients.