The Role of Ferroptosis in Gastric Cancer

Abstract

Md Foysal Uddin Sarker Shanto, Xu Zhitao, Sahar Saberi, Samiul Haque, Chagouri Bayan, Atefeh Bahrami, Chamse Doha Khodri, Hussein Mudher Ali Al Tameemi, Intisar Kalam Ispak, Tahsin Hannan, Md Shakib Uddin Sarker Joy

Ferroptosis is a unique type of controlled cell death that is dependent on iron and is distinguished by the buildup of lipid peroxides. Its distinct morphological, biochemical, and genetic traits set it apart from other types of cell death, including necrosis, autophagy, and apoptosis. Recent research has shown its crucial role in the development, progression, and emergence of treatment resistance in a number of cancers, most notably Gastric cancer (GC), a highly morbid and fatal disease that is common around the world. With an emphasis on iron metabolism, lipid peroxidation, and the critical regulatory functions of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long-chain family member 4 (ACSL4), this review provides a thorough investigation of the molecular mechanisms underlying ferroptosis. It also looks at how oncogenes, such as p53, KRAS, and MYC, and tumor suppressors affect ferroptosis sensitivity. The review also addresses ferroptosis’s important therapeutic implications in GC and emphasizes its emerging significance in overcoming chemoresistance. The ability to promote ferroptosis and enhance the effectiveness of well-established chemotherapy and immunotherapy procedures has been shown for both natural substances, such as curcumin and artesunate, and synthetic drugs, such as erastin and RSL3. The essential functions of non-coding RNAs, particularly circular RNAs (circRNAs), long non-coding (lncRNAs), and microRNAs, in modifying ferroptosis pathways are also clarified, indicating their potential as useful biomarkers and prospective therapeutic targets. Despite these significant advancements, systemic toxicity, lack of selectivity, and the complex effect of the tumor microenvironment remain obstacles to the clinical translation of ferroptosis-based treatments. Thus, this analysis highlights the urgent need for more thorough research into new ferroptosis-based treatments and the creation of reliable prognostic biomarkers. In the end, Ferroptosis targeting is a very promising approach to improving the results of GC treatment and making it easier to apply individualized therapeutic measures.

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