Molecular Mechanisms and Novel Therapeutics Targeting Ferroptosis in Gastric Cancer: A Literature Review

Since the discovery of ferroptosis, which plays an important role in gastric cancer (GC), its activation has been crucial for developing tumor therapeutic strategies. Recently, ferroptosis activation has become a research hotspot for GC treatment approaches. Energy and metabolism dysfunctions involving lipids, amino acids, iron, sugars, and nucleotides caused by GC cells in a typical hypoxic microenvironment are important disease characteristics. However, the immune escape mechanism of GC cells limits the occurrence of programed cell death, a controllable form of which is ferroptosis. First, excessive reactive oxygen species production induces changes in intracellular iron ion levels, resulting in an imbalance in the antioxidant defense system. Finally, excessive accumulation of intracellular lipid peroxidation byproducts destroys cell membrane consistency and causes cell death. The promotion of ferroptosis in GC cells has been widely employed as a method for inhibiting tumor growth and chemotherapy resistance, which is helpful for developing anti-GC targeted treatments. Because GC cells are sensitive to ferroptosis-inducing agents, some traditional antitumor drugs (e.g., cisplatin) and Chinese herbal or natural medicines (e.g., artemisinin) exert anticancer effects by inducing this process. In this article, we summarize the basic molecular mechanisms underlying ferroptosis and the involved tumor markers, along with associated chemotherapy drugs and natural medicines. To activate ferroptosis in GC, new targeted drug therapies can be used within the clinical treatment field to kill GC cells and enhance tumor sensitivity to chemotherapy.