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Unleashing Ferroptosis in Human Cancers: Targeting Ferroptosis Suppressor Protein 1 for Overcoming Therapy Resistance
1Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do 13496, Republic of Korea.
Abstract:
Ferroptosis, a recently identified form of regulated cell death characterized by the iron-dependent accumulation of lethal lipid peroxidation, has gained increasing attention in cancer therapy. Ferroptosis suppressor protein 1 (FSP1), an NAD(P)H-ubiquinone oxidoreductase that reduces ubiquinone to ubiquinol, has emerged as a critical player in the regulation of ferroptosis. FSP1 operates independently of the canonical system xc-/glutathione peroxidase 4 pathway, making it a promising target for inducing ferroptosis in cancer cells and overcoming ferroptosis resistance. This review provides a comprehensive overview of FSP1 and ferroptosis, emphasizing the importance of FSP1 modulation and its potential as a therapeutic target in cancer treatment. We also discuss recent progress in developing FSP1 inhibitors and their implications for cancer therapy. Despite the challenges associated with targeting FSP1, advances in this field may provide a strong foundation for developing innovative and effective treatments for cancer and other diseases.
Insights
Ferroptosis suppressor protein 1 (FSP1) regulates cell death via lipid peroxidation. Targeting FSP1 offers a new strategy to induce ferroptosis and combat cancer resistance.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Ferroptosis is a regulated cell death pathway driven by iron-dependent lipid peroxidation.
- Ferroptosis suppressor protein 1 (FSP1) is a key regulator of ferroptosis, acting independently of other known pathways.
- FSP1's role presents a novel therapeutic avenue for cancer treatment.
Purpose of the Study:
- To provide a comprehensive review of FSP1 and its role in ferroptosis.
- To highlight the therapeutic potential of modulating FSP1 in cancer.
- To discuss the development and implications of FSP1 inhibitors.
Main Methods:
- Literature review of ferroptosis and FSP1.
- Analysis of FSP1's biochemical function as an NAD(P)H-ubiquinone oxidoreductase.
- Review of current research on FSP1 inhibitors and their preclinical/clinical relevance.
Main Results:
- FSP1 critically regulates ferroptosis by reducing ubiquinone to ubiquinol.
- FSP1 functions independently of the canonical system xc-/GPX4 pathway.
- FSP1 inhibition shows promise in overcoming cancer ferroptosis resistance.
Conclusions:
- FSP1 is a significant therapeutic target for inducing ferroptosis in cancer.
- Developing FSP1 inhibitors is crucial for advancing cancer therapy.
- Targeting FSP1 may lead to innovative treatments for various diseases.
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