Targeting ferroptosis in gastric cancer: Strategies and opportunities

Abstract

SummaryFerroptosis is a novel form of programmed cell death morphologically, genetically, and biochemically distinct from other cell death pathways and characterized by the accumulation of iron‐dependent lipid peroxides and oxidative damage. It is now understood that ferroptosis plays an essential role in various biological processes, especially in the metabolism of iron, lipids, and amino acids. Gastric cancer (GC) is a prevalent malignant tumor worldwide with low early diagnosis rates and high metastasis rates, accounting for its relatively poor prognosis. Although chemotherapy is commonly used to treat GC, drug resistance often leads to poor therapeutic outcomes. In the last several years, extensive research on ferroptosis has highlighted its significant potential in GC therapy, providing a promising strategy to address drug resistance associated with standard cancer therapies. In this review, we offer an extensive summary of the key regulatory factors related to the mechanisms underlying ferroptosis. Various inducers and inhibitors specifically targeting ferroptosis are uncovered. Additionally, we explore the prospective applications and outcomes of these agents in the field of GC therapy, emphasizing their capacity to improve the outcomes of this patient population.

Ferroptosis: a promising target for fumarate hydratase-deficient tumor therapeutics literature review

“…Mitochondria, the core organelles that control metabolism and produce ROS, are closely related to ferroptosis ( 17 ). Ferroptosis involvement in multiple human diseases has been established, such as gastric cancer, kidney diseases, and Alzheimer’s disease ( 29 - 31 ). These findings suggest that modulating ferroptosis might be potential therapeutic approaches in treating cancer or other diseases.…”

Oxaliplatin-Loaded Mil-100(Fe) for Chemotherapy–Ferroptosis Combined Therapy for Gastric Cancer

“…In the MOF structure, coordination bonds play a supporting role as a skeleton, and the loading of chemotherapy drugs in MOF is through physical adhesion or hydrogen bonding, π–π interaction, etc. − The above-mentioned supramolecular weak interaction is not as stable as a covalent bond, which provides a possibility for the responsive disintegration of the MOF structure and the responsive release of chemotherapy drugs. In addition, ferroptosis-related research has developed rapidly in recent years, and has been well applied in the field of tumor therapy. − Ferroptosis is an iron-dependent programmed cell death involving intracellular iron accumulation, oxidation–reduction (REDOX) imbalance, and lipid peroxidation. − Using iron-containing MOF as a chemotherapy drug carrier is also expected to take advantage of the interaction between iron ions and tumor microenvironment (TME) components, resulting in excessive accumulation of lipid peroxides (LPO) and reactive oxygen species (ROS), resulting in a new therapeutic function of ferroptosis.…”

Ciprofloxacin is a novel anti-ferroptotic antibiotic

“…Furthermore, multiple GPX4-independent pathways have been reported to bolster the defense against ferroptosis in a context-dependent manner [ 4 ]. Despite ongoing research, the full scope of ferroptosis in health and disease remains incompletely understood, rendering it a vital focus in tumor therapy [ [9] , [10] , [11] , [12] ].…”